2024/10/14 更新

写真a

キタカゼ トモヤ
北風 智也
Kitakaze Tomoya
担当
大学院農学研究科 生命機能化学専攻 助教
農学部 生命機能化学科
職名
助教
所属
農学研究院
ホームページ
所属キャンパス
中百舌鳥キャンパス

担当・職階

  • 大学院農学研究科 生命機能化学専攻 

    助教  2022年04月 - 継続中

  • 農学部 生命機能化学科 

    助教  2022年04月 - 継続中

取得学位

  • 博士(応用生命科学) ( 大阪府立大学 )

研究分野

  • ライフサイエンス / 食品科学

研究キーワード

  • 栄養生化学

  • 分子栄養学

研究概要

  • 機能性食品因子に関する研究

  • マイオカインに関する研究

  • ビタミンAの生理作用に関する研究

所属学協会

  • 日本分子生物学会

    2018年 - 継続中

  • 日本フードファクター学会

    2017年 - 継続中

  • 日本農芸化学会

    2014年 - 継続中

  • 日本ビタミン学会

    2013年 - 継続中

  • 日本栄養・食糧学会

    2012年 - 継続中

受賞歴

  • 奨励賞

    北風智也

    2022年06月   日本栄養・食糧学会   食品因子の薬物代謝系を介した生体防御機能に関する研究

職務経歴(学外)

  • 大阪公立大学大学院   農学研究科

    2022年04月 - 継続中

  • 大阪府立大学大学院   生命環境科学研究科

    2021年04月 - 2022年03月

  • 神戸大学大学院   農学研究科

    2020年03月 - 2021年03月

  • 神戸大学大学院   農学研究科   学術研究員

    2019年04月 - 2020年02月

  • 神戸大学大学院   科学技術イノベーション研究科   学術研究員

    2017年04月 - 2019年03月

論文

  • Mogrol stimulates G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and insulin secretion from pancreatic β-cells and alleviates hyperglycemia in mice

    Tanaka C.

    Scientific Reports   14 ( 1 )   3244   2024年12月

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  • Single oral administration of quercetin glycosides prevented acute hyperglycemia by promoting GLUT4 translocation in skeletal muscles through the activation of AMPK in mice

    Journal of Clinical Biochemistry and Nutrition   74 ( 1 )   37 - 46   2024年( ISSN:09120009 ( eISSN:18805086

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国内誌  

    DOI: 10.3164/jcbn.23-30

    PubMed

  • Mung bean peptides promote glucose uptake via Jak2 activation in L6 myotubes.

    Yasukiyo Yoshioka, Qing Zhang, Xin Wang, Tomoya Kitakaze, Yoko Yamashita, Mitsutaka Kohno, Hitoshi Ashida

    Food & function   2023年05月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Mung beans are among the important edible legumes cultivated in Asia, Southern Europe, and Northern America. Mung beans contain 20-30% proteins with high digestibility and possess biological activities, but detailed health beneficial functions are not fully understood yet. In this study, we report the isolation and identification of active peptides from mung beans which promote glucose uptake and elucidate their mechanism in L6 myotubes. HTL, FLSSTEAQQSY, and TLVNPDGRDSY were isolated and identified as active peptides. These peptides promoted the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. The tripeptide HTL promoted glucose uptake through the activation of adenosine monophosphate-activated protein kinase, while the oligopeptides FLSSTEAQQSY and TLVNPDGRDSY through the activation of the PI3K/Akt pathway. Furthermore, these peptides promoted the phosphorylation of Jak2 via interaction with the leptin receptor. Thus, mung bean is a promising functional food for the prevention of hyperglycemia and type 2 diabetes through promoting glucose uptake accompanied by JAK2 activation in the muscle cells.

    DOI: 10.1039/d3fo00836c

    PubMed

  • All-Trans Retinoic Acid-Responsive LGR6 Is Transiently Expressed during Myogenic Differentiation and Is Required for Myoblast Differentiation and Fusion

    Kitakaze T.

    International Journal of Molecular Sciences   24 ( 10 )   2023年05月( ISSN:16616596

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  • Aged Garlic Extract Prevents Alcohol-Induced Cytotoxicity through Induction of Aldehyde Dehydrogenase 2 in the Liver of Mice.

    Kitakaze T, Inoue M, Ashida H

    Molecular nutrition & food research   e2200627   2023年03月( ISSN:1613-4125

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    DOI: 10.1002/mnfr.202200627

    PubMed

  • 卵巣老化のメカニズムと食品成分による予防 査読

    田中 千智, 北風 智也, 原田 直樹, 山地 亮一

    ビタミン   97 ( 2 )   79 - 83   2023年02月( ISSN:0006386X ( eISSN:2424080X

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  • Transport Form and Pathway from the Intestine to the Peripheral Tissues and the Intestinal Absorption and Metabolism Properties of Oleamide 査読

    Kobayashi Y.

    Journal of Agricultural and Food Chemistry   70 ( 49 )   15499 - 15508   2022年12月( ISSN:0021-8561 ( eISSN:1520-5118

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.jafc.2c06791

    PubMed

  • Androgen receptor suppresses β-adrenoceptor-mediated CREB activation and thermogenesis in brown adipose tissue of male mice 査読

    Harada N.

    Journal of Biological Chemistry   298 ( 12 )   102619 - 102619   2022年10月( ISSN:00219258

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    DOI: 10.1016/j.jbc.2022.102619

    PubMed

  • Carotenoid transporter CD36 expression depends on hypoxia-inducible factor-1α in mouse soleus muscles(和訳中)

    Kitakaze Tomoya, Sugihara Takashi, Kameyama Hiromichi, Maruchi Asami, Kobayashi Yasuyuki, Harada Naoki, Yamaji Ryoichi

    Journal of Clinical Biochemistry and Nutrition   71 ( 2 )   112 - 121   2022年09月( ISSN:0912-0009

  • Dietary oleamide attenuates obesity induced by housing mice in small cages(和訳中)

    Kobayashi Yasuyuki, Kubota Mai, Sugimoto Keiichiro, Kitakaze Tomoya, Harada Naoki, Yamaji Ryoichi

    Bioscience, Biotechnology, and Biochemistry   86 ( 8 )   1095 - 1105   2022年08月( ISSN:0916-8451

  • Dietary oleamide attenuates obesity induced by housing mice in small cages. 査読

    Yasuyuki Kobayashi, Mai Kubota, Keiichiro Sugimoto, Tomoya Kitakaze, Naoki Harada, Ryoichi Yamaji

    Bioscience, biotechnology, and biochemistry   2022年05月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Physical inactivity due to prolonged sedentary behavior induces obesity. Therefore, we investigated whether housing mice in small cages to mimic sedentary behavior induced obesity and whether dietary oleamide (cis-9,10-octadeceneamide) suppressed the induced obesity. A single oral administration of oleamide (50 mg/kg) to mice resulted in the accumulation of the exogenous oleamide in abdominal visceral fat. Next, mice were housed in small cages and oleamide (50 mg/kg/d) was orally administered for 12 weeks. Housing mice in small cages impaired glucose tolerance and increased food efficiency. It also increased body weight and abdominal fat mass. Dietary oleamide improved the impairment and inhibited their increases in mice housed in small cages. Furthermore, dietary oleamide suppressed the mRNA expression of inflammation-related factors in abdominal fat of mice housed in small cages. Hence, these results indicate that although housing mice in small cages induces obesity and increases abdominal fat mass, dietary oleamide suppresses the obesity.

    DOI: 10.1093/bbb/zbac082

    PubMed

  • Pectolinarigenin Induces Antioxidant Enzymes through Nrf2/ARE Pathway in HepG2 Cells. 査読

    Mariko Shiraiwa, Tomoya Kitakaze, Yoko Yamashita, Yuichi Ukawa, Katsuyuki Mukai, Hitoshi Ashida

    Antioxidants (Basel, Switzerland)   11 ( 4 )   2022年03月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Pectolinarigenin (PG) and its glycoside pectolinarin (PN) were reported to have various health beneficial functions such as anti-inflammatory and anti-carcinogenic activities. It has also been reported that PG and PN have radical scavenging ability as direct antioxidant activity. However, the indirect antioxidant activity of PG and PN by inducing antioxidant enzymes in hepatocytes is not fully understood yet. In this study, we investigated whether PG and PN increase expression of antioxidant enzymes through the nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated pathway in human hepatoma HepG2 cells and the liver of male ICR mice. PG, but not PN, induced antioxidant enzymes, namely heme oxigenase-1, NAD(P)H:quinone oxidoreductase 1, and aldo-keto reductase family 1 member B10, in HepG2 cells. As for the induction mechanism of these enzymes, PG-induced nuclear accumulation of Nrf2 increased antioxidant response element (ARE)-mediated transcriptional activity and suppressed degradation of Nrf2 through modification of Kelch-like EXH-associated protein 1. Oral administration of PG also induced nuclear accumulation Nrf2 and expression of antioxidant enzymes in the liver of mice. Therefore, PG, but not PN, exhibits the indirect antioxidant activity by inducing antioxidant enzymes through the Nrf2/ARE pathway and may protect liver from oxidative stress.

    DOI: 10.3390/antiox11040675

    PubMed

  • Curcumin activates G protein-coupled receptor 97 (GPR97) in a manner different from glucocorticoid. 査読

    Naoki Harada, Yumi Arahori, Mai Okuyama, Paula B Luis, Akil I Joseph, Tomoya Kitakaze, Naoki Goshima, Claus Schneider, Hiroshi Inui, Ryoichi Yamaji

    Biochemical and biophysical research communications   595   41 - 46   2022年01月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Curcumin is a yellow pigment in turmeric (Curcuma longa) with various physiological effects in the body. To elucidate the molecular mechanisms by which bioactive compounds exert their function, identification of their molecular targets is crucial. In this study, we show that curcumin activates G protein-coupled receptor 97 (GPR97). Curcumin dose-dependently activated serum-response element-, but not serum-response factor-response element-, nuclear factor of activated T-cell-response element-, or cAMP-response element-, mediated transcription in cells overexpressed with GPR97. The structure-activity relationship indicated that (i) the double-bonds of the central 7-carbon chain were essential for activation; (ii) a methoxy group on the aromatic ring was required for maximal activity; (iii) the addition of glucuronic acid moiety or a methoxy group to the aromatic ring, but not the methylation of the aromatic p-hydroxy group, eliminated the activity; (iv) the stability of curcumin would be related to receptor activation. Both mutant GPR97(T250A) lacking the cleavage at GPCR proteolysis site and mutant GPR97(ΔN) lacking the N-terminal extracellular region were activated by curcumin and its related compounds similar to wild-type GPR97. In contrast, the synthetic glucocorticoid beclomethasone dipropionate and l-Phe activated wild-type GPR97 and GPR97(T250A), but not GPR97(ΔN). Moreover, curcumin exerted an additive effect on the activation of wild-type GPR97 with beclomethasone dipropionate, but not with l-Phe. Taken together, these results indicate that curcumin activates GPR97 coupled to Gi/Go subunit, and suggest that curcumin and glucocorticoid activate GPR97 in a different manner.

    DOI: 10.1016/j.bbrc.2022.01.075

    PubMed

  • Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin. 査読

    Naoki Harada, Mai Okuyama, Yoshiaki Teraoka, Yumi Arahori, Yoh Shinmori, Hiroko Horiuchi, Paula B Luis, Akil I Joseph, Tomoya Kitakaze, Shigenobu Matsumura, Tohru Hira, Norio Yamamoto, Takashi Iuni, Naoki Goshima, Claus Schneider, Hiroshi Inui, Ryoichi Yamaji

    NPJ science of food   6 ( 1 )   4 - 4   2022年01月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    The identification of molecular targets of bioactive food components is important to understand the mechanistic aspect of their physiological functions. Here, we have developed a screening system that enables us to determine the activation of G protein-coupled receptors (GPCRs) by food components and have identified GPR55 as a target for curcumin. Curcumin activated GPR55 and induced serum-response element- and serum-response factor-mediated transcription, which were inhibited by Rho kinase and GPR55 antagonists. Both the methoxy group and the heptadienone moiety of curcumin were required for GPR55 activation. The F1905.47 residue of GPR55 was important for the interaction with curcumin. The curcumin-induced secretion of glucagon-like peptide-1 in GLUTag cells was inhibited by a GPR55 antagonist. These results indicate that expression screening is a useful system to identify GPCRs as targets of food components and strongly suggest that curcumin activates GPR55 as an agonist, which is involved in the physiological function of curcumin.

    DOI: 10.1038/s41538-021-00119-x

    PubMed

  • Preventive effects of black soybean polyphenols on non-alcoholic fatty liver disease in three different mouse models. 査読

    Mio Yamamoto, Yasukiyo Yoshioka, Tomoya Kitakaze, Yoko Yamashita, Hitoshi Ashida

    Food & function   13 ( 2 )   1000 - 1014   2022年01月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), are a major health issue throughout the world. Certain food components such as polyphenols are expected to possess preventive effects on NAFLD and NASH. In this study, the preventive effects of black soybean polyphenols were examined by using three NAFLD/NASH animal models. In a choline-deficient and L-amino acid-defined high-fat diet-induced NASH model, the intake of black soybean polyphenols decreased oxidative stress, but failed in attenuating liver injury and decreasing the expression of alpha-smooth muscle actin (α-SMA). In a Western diet with sucrose and fructose containing sweetened water-induced NAFLD model, black soybean polyphenols suppressed hepatic lipid accumulation, oxidative stress, aminotransferase activities in the plasma, inflammatory cytokine expression, and α-SMA expression accompanied by modulation of lipid metabolism. In a combination of Western diet and carbon tetrachloride model, black soybean polyphenols also suppressed hepatic lipid accumulation, oxidative stress, aminotransferase activities in the plasma, and α-SMA expression. In conclusion, black soybean is an attractive food for the prevention of NAFLD and NASH due to its strong antioxidant activity.

    DOI: 10.1039/d1fo03541j

    PubMed

  • Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin 査読

    Naoki Harada, Mai Okuyama, Yoshiaki Teraoka, Yumi Arahori, Yoh Shinmori, Hiroko Horiuchi, Paula B Luis, Akil I Joseph, Tomoya Kitakaze, Shigenobu Matsumura, Tohru Hira, Norio Yamamoto, Takashi Iuni, Naoki Goshima, Claus Schneider, Hiroshi Inui, Ryoichi Yamaji

    NPJ Sci. Food 雑誌   2022年01月

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    共著区分:共著  

  • Preventive effects of black soybean polyphenols on non-alcoholic fatty liver disease in three different mouse models 査読

    Mio Yamamoto, Yasukiyo Yoshioka, Tomoya Kitakaze, Yoko Yamashita, Hitoshi Ashida

    Food Funct.   2022年01月

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    共著区分:共著  

  • 食品因子の薬物代謝系を介した生体防御機能に関する研究

    北風 智也

    日本栄養・食糧学会誌   75 ( 6 )   291 - 296   2022年( ISSN:02873516 ( eISSN:18832849

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    <p>生体外異物であるダイオキシン類による毒性はアリール炭化水素受容体 (AhR) を介した作用であるため, AhRの活性化を抑制することが毒性の緩和につながる。ダイオキシン類の毒性の緩和は転写因子nuclear factor-erythroid 2-related factor 2 (Nrf2) を介した薬物代謝第Ⅱ相酵素の誘導も有効である。Nrf2の活性化はダイオキシン類の暴露以外の環境ストレスに対する生体防御機能も高める。そのため, AhRを抑制しNrf2を活性化する食品因子の探索を行ってきた。筆者はこれまでに, フラボノイドであるルテオリンとケンフェロールの共作用がAhRの活性抑制効果を増強すること, 日常的な食事から摂取可能な量のルテオリンがNrf2を活性化することを明らかにした。また, AhRの活性化が引き起こす肝臓への脂肪蓄積が, 概日リズムの乱れに起因することと, ルテオリンとケンフェロールによる抑制効果を見出した。これらのことから, ルテオリンとケンフェロールは薬物代謝系を介した生体外異物に対する生体防御機能に関して, 有効性が明らかとなった。</p>

    DOI: 10.4327/jsnfs.75.291

  • Carotenoid transporter CD36 expression depends on hypoxia-inducible factor-1α in mouse soleus muscles 査読

    Tomoya Kitakaze, Takashi Sugihira, Hiromichi Kameyama, Asami Maruchi, Yasuyuki Kobayashi, Naoki Harada, Ryoichi Yamaji

    Journal of Clinical Biochemistry and Nutrition   71 ( 2 )   112 - 121   2022年( ISSN:0912-0009 ( eISSN:1880-5086

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3164/jcbn.21-163

  • Oleamide rescues tibialis anterior muscle atrophy of mice housed in small cages. 査読

    Yasuyuki Kobayashi, Natsumi Watanabe, Tomoya Kitakaze, Keiichiro Sugimoto, Takeshi Izawa, Kenji Kai, Naoki Harada, Ryoichi Yamaji

    The British journal of nutrition   126 ( 4 )   481 - 491   2021年08月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Skeletal muscle atrophy causes decreased physical activity and increased risk of metabolic diseases. We investigated the effects of oleamide (cis-9,10-octadecanamide) treatment on skeletal muscle health. The plasma concentration of endogenous oleamide was approximately 30 nM in the male ddY mice under normal physiological conditions. When the stable isotope-labelled oleamide was orally administered to male ddY mice (50 mg/kg), the plasma concentration of exogenous oleamide reached approximately 170 nM after 1 h. Male ddY mice were housed in small cages (one-sixth of normal size) to enforce sedentary behaviour and orally administered oleamide (50 mg/kg/day) for 4 weeks. Housing in small cages decreased tibialis anterior (TA) muscle mass and the cross-sectional area (CSA) of the myofibres in TA muscle. Dietary oleamide alleviated the decreases in TA muscle and resulted in plasma oleamide concentration of approximately 120 nM in mice housed in small cages. Housing in small cages had no influence on the phosphorylation levels of Akt, mTOR, and p70S6K in TA muscle; nevertheless, oleamide increased the phosphorylation levels of the proteins. Housing in small cages increased the expression of LC3-II and p62, but not LC3-I, in TA muscle, and oleamide reduced LC3-I, LC3-II, and p62 expression levels. In C2C12 myotubes, oleamide increased myotube diameter at ≥ 100 nM. Furthermore, the mTOR inhibitor, Torin 1, suppressed oleamide-induced increases in myotube diameter and protein synthesis. These results indicate that dietary oleamide rescued TA muscle atrophy in mice housed in small cages, possibly by activating the PI3K/Akt/mTOR signalling pathway and restoring autophagy flux.

    DOI: 10.1017/S0007114520004304

    PubMed

  • Oleamide rescues tibialis anterior muscle atrophy of mice housed in small cages

    Yasuyuki Kobayashi, Natsumi Watanabe, Tomoya Kitakaze, Keiichiro Sugimoto, Kenji Kai, Kaoki Harada, Ryoichi Yamaji.

    Br. J. Nutr.   2020年12月

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    共著区分:共著  

  • Kaempferol Promotes Glucose Uptake in Myotubes through a JAK2-Dependent Pathway. 査読

    Tomoya Kitakaze, Hao Jiang, Takuya Nomura, Ken-Yu Hironao, Yoko Yamashita, Hitoshi Ashida

    Journal of agricultural and food chemistry   68 ( 47 )   13720 - 13729   2020年11月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Kaempferol possesses various health-promoting functions including antihyperglycemic activity, but its underlying molecular mechanism is poorly understood. Glucose transporter 4 (GLUT4) plays an important role in the uptake of blood glucose into muscle cells after its translocation to the plasma membrane. In this study, we demonstrated that kaempferol at 1.0 nM or more significantly increased the uptake of 2-[3H]- deoxy-d-glucose by 1.3-1.4-fold in L6 myotubes. Kaempferol at 10 pM or more also significantly increased GLUT4 translocation by 1.3-1.6-fold. Kaempferol at 1.0 nM significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) by 2.9-fold, liver kinase B1 and Janus kinase 2 (JAK2) by 1.9-fold, and signal transducer and activator of transcription 3 by 3.7-fold. In addition, kaempferol increased phosphorylation of phosphoinositide 3-kinase (PI3K) by 1.8-fold but not the insulin receptor. Small interfering RNA (siRNA) for AMPK, JAK2, or PI3K canceled kaempferol-induced glucose uptake and GLUT4 translocation. Furthermore, siRNA for JAK2 canceled kaempferol-induced phosphorylation of AMPK and PI3K. These results indicate that a JAK2-depdendent pathway regulates kaempferol-induced glucose uptake and GLUT4 translocation in L6 myotubes and that kaempferol may be an effective compound for the prevention of hyperglycemia.

    DOI: 10.1021/acs.jafc.0c05236

    PubMed

  • Kaempferol promotes glucose uptake in myotubes through JAK2-dependent pathway

    Tomoya Kitakaze, Hao Jiang, Takuya Nomura, Ken-yu Hironao, Yoko Yamashita, Hitoshi ashida.

    J. Agric. Food Chem.   2020年11月

  • β-Cryptoxanthin Improves p62 Accumulation and Muscle Atrophy in the Soleus Muscle of Senescence-Accelerated Mouse-Prone 1 Mice. 査読

    Mari Noguchi, Tomoya Kitakaze, Yasuyuki Kobayashi, Katsuyuki Mukai, Naoki Harada, Ryoichi Yamaji

    Nutrients   12 ( 8 )   2020年07月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    We investigated the effects of β-cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or β-cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. β-cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice; however, β-cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice; however, β-cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. β-cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, β-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the β-cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that β-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

    DOI: 10.3390/nu12082180

    PubMed

  • Bisacurone suppresses hepatic lipid accumulation through inhibiting lipogenesis and promoting lipolysis

    Hitoshi Ashida, Xiaokuo Tian, Tomoya Kitakaze, Yoko Yamashita.

    J. Clin. Biochem. Nutr.   2020年07月

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    共著区分:共著  

  • Enzymatically synthesized glycogen inhibited degranulation and inflammatory responses through stimulation of intestine

    Yasukiyo Yoshioka, Masako Inoue, Hiroko Yoshioka, Tomoya Kitakaze, Takashi Furuyashiki, Naoki Abe, Hitoshi Ashida.

    J. Clin. Biochem. Nutr.   2020年07月

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    共著区分:共著  

  • Enzymatically synthesized glycogen protects inflammation induced by urban particulate matter in normal human epidermal keratinocytes

    Tomoya Kitakaze, Yasukiyo Yoshioka, Takashi Furuyashiki, Hitoshi Ashida.

    J. Clin. Biochem. Nutr.   2020年07月

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    共著区分:共著  

  • Enzymatically synthesized glycogen prevents UVB-induced cell damage in normal human epidermal keratinocytes

    Yasukiyo Yoshioka, Tomoya Kitakaze, Takakazu Mitani, Takashi Furuyashiki, Hitoshi Ashida.

    J. Clin. Biochem. Nutr.   2020年07月

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    共著区分:共著  

  • Prevention effect of quercetin and its glycosides on obesity and hyperglycemia through activating AMPKα in high-fat diet-fed ICR mice

    Hao Jiang, Yuko Horiuchi, Ken-yu Hironao, Tomoya Kitakaze, Yoko Yamashita, Hitoshi Ashida.

    J. Clin. Biochem. Nutr.   2020年07月

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    共著区分:共著  

  • β-Cryptoxanthin improves p62 accumulation and muscle atrophy in the soleus muscle of senescence-accelerated mouse-prone 1 mice

    Mari Noguchi†, Tomoya Kitakaze†, Yasuyuki Kobayashi, Katsuyuki Mukai, Naoki Harada, Ryoichi Yamaji.

    Nutrients   2020年07月

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    共著区分:共著  

  • Enzymatically synthesized glycogen inhibited degranulation and inflammatory responses through stimulation of intestine. 査読

    Yasukiyo Yoshioka, Masako Inoue, Hiroko Yoshioka, Tomoya Kitakaze, Takashi Furuyashiki, Naoki Abe, Hitoshi Ashida

    Journal of clinical biochemistry and nutrition   67 ( 1 )   67 - 73   2020年07月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国内誌  

    The patients of type I allergic diseases were increased in the developed countries. Recently, many studies have focused on food factors with anti-allergic activities. Enzymatically synthesized glycogen, a polysaccharide with a multi-branched α-1,4 and α-1,6 linkages, is a commercially available product from natural plant starch, and has immunostimulation activity. However, effect of enzymatically synthesized glycogen on the anti-allergic activity was unclear yet. In this study, we investigated that enzymatically synthesized glycogen inhibited allergic and inflammatory responses using a co-culture system consisting of Caco-2 and RBL-2H3 cells. Enzymatically synthesized glycogen inhibited antigen-induced β-hexosaminidase release and production of TNF-α and IL-6 in RBL-2H3 cells in the co-culture system. Furthermore, enzymatically synthesized glycogen inhibited antigen-induced phosphorylation of tyrosine kinases, phospholipase C γ1/2, mitogen-activated protein kinases and Akt. Anti-allergic and anti-inflammatory activities of enzymatically synthesized glycogen were indirect action through stimulating Caco-2 cells, but not by the direct interaction with RBL-2H3 cells, because enzymatically synthesized glycogen did not permeate Caco-2 cells. These findings suggest that enzymatically synthesized glycogen is an effective food ingredient for prevention of type I allergy through stimulating the intestinal cells.

    DOI: 10.3164/jcbn.20-33

    PubMed

  • 酵素合成グリコーゲンは腸管の刺激を介して脱顆粒と炎症反応を阻害する(Enzymatically synthesized glycogen inhibited degranulation and inflammatory responses through stimulation of intestine)

    Yoshioka Yasukiyo, Inoue Masako, Yoshioka Hiroko, Kitakaze Tomoya, Furuyashiki Takashi, Abe Naoki, Ashida Hitoshi

    Journal of Clinical Biochemistry and Nutrition   67 ( 1 )   67 - 73   2020年07月( ISSN:0912-0009

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    酵素合成グリコーゲン(ESG)の抗アレルギー効果を共培養システムで調べた。Caco-2細胞付着トランズウェルインサートプレートをRBL-2H3またはBMMC細胞プレートウェルに挿入した。ESGを上部に加えて培養後、RBL-2H3またはBMMC細胞の側底部を抗DNP-IgEに感作させ、DNP-BSAで攻撃した。ESG添加により、用量依存的にCaco-2/RBL-2H3共培養のRBL-2H3細胞からのβヘキソサミニダーゼ放出が抑制された。共培養のBMMC細胞からのβヘキソサミニダーゼ放出も同様に抑制された。RBL-2H3細胞からのβヘキソサミニダーゼ放出に及ぼすESGの直接的抑制効果は共培養の場合より低かった。ESGの直接処理はBMMC細胞からのβヘキソサミニダーゼ放出に影響を与えなかった。ESG処理により、共培養のRBL-2H3細胞におけるLyn、Syk、PLCγ1/2のリン酸化、TNF-αとIL-6の産生、JNK/p38/Aktのリン酸化が有意に抑制された。ESGはCaco-2細胞を浸透しないことが示唆された。CaCo-2/RBL-2H3共培養へのESG添加により、Caco-2細胞から分泌された未知因子の刺激を介して、RBL-2H3細胞における脱顆粒マーカーの放出と炎症性サイトカイン産生のシグナル伝達に必須のSykの活性化が抑制されることが推測された。

  • 酵素合成グリコーゲンは紫外線Bによって生じた正常ヒト表皮角化細胞の障害を防ぐ(Enzymatically synthesized glycogen prevents ultraviolet B-induced cell damage in normal human epidermal keratinocytes)

    Yoshioka Yasukiyo, Kitakaze Tomoya, Mitani Takakazu, Furuyashiki Takashi, Ashida Hitoshi

    Journal of Clinical Biochemistry and Nutrition   67 ( 1 )   36 - 42   2020年07月( ISSN:0912-0009

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    紫外線B(UVB)照射による正常ヒト表皮角化細胞(NHEK)内の活性酸素種(ROS)蓄積とアポトーシスに対する酵素合成グリコーゲン(ESG)の抑制作用を調べた。ESG、ESG代謝物(RG)、カキ由来グリコーゲン(OG)を試験に用いた。UVB照射によりNHEK内のROS蓄積量が増加した。ESGとRGはUVBが誘導したROS蓄積を用量依存的に阻害したが、OGには阻害作用はみられなかった。ESGとRG処理はHO-1、NQO1、Nrf2の蛋白質発現レベルを上昇させたが、OGには上昇作用はみられなかった。ESGとRGはNrf2遺伝子発現に影響を及ぼさなかった。Nrf2は時間依存的にシクロヘキシミド処理により分解されたが、ESGとRGはNHEK内のNrf2分解を阻害した。ESGとRG処理はNrf2のセリン残基のリン酸化を促進した。RNA干渉によるHO-1とNQO1両方のノックダウンは、UVBが誘導したROS蓄積に対してESGが惹起した抗酸化作用を完全に無効にした。蛍光発生ペプチド基質を用いた酵素活性アッセイにより、UVB照射はNHEK内のカスパーゼ3および9の活性を上昇させたが、カスパーゼ8は活性化されなかった。ESGとRGはUVBにより上昇したカスパーゼ3および9活性を阻害したが、OGは阻害しなかった。ESGとRGはUVBに起因する細胞毒性とDNA断片化を阻害した。

  • Bisacurone suppresses hepatic lipid accumulation through inhibiting lipogenesis and promoting lipolysis. 査読

    Hitoshi Ashida, Xiaokuo Tian, Tomoya Kitakaze, Yoko Yamashita

    Journal of clinical biochemistry and nutrition   67 ( 1 )   43 - 52   2020年07月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国内誌  

    Turmeric and its components have various health beneficial functions. However, little is known about function of bisacurone, which is one of the sesquiterpenes in turmeric, at the compound level. In this study, we investigated the preventive effect of bisacurone on hepatic lipid accumulation and its mechanism in HepG2 cells and ICR mice. In HepG2 cells, bisacurone significantly inhibited fatty acid-induced intracellular lipid accumulation in a dose-dependent manner. Bisacurone at 10 µM increased protein expression of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1A accompanied by phosphorylation of AMP-activated protein kinase. In the liver of ICR mice, bisacurone decreased total lipids, triglyceride, and cholesterol contents. Bisacurone at 10 mg/kg body weight increased phosphorylation of AMP-activated protein kinase, and its downstream acetyl-CoA carboxylase as a rate-limiting enzyme for lipogenesis, while it decreased the nuclear translocation level of sterol regulatory element-binding protein 1 and carbohydrate-responsive element-binding protein as the major transcription factors for lipogenesis. On the other hand, bisacurone promoted lipolysis by up-expression of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1A. Thus, bisacurone might be a valuable food factor for preventing hepatic lipid accumulation by inhibiting lipogenesis and promoting lipolysis through phosphorylation of AMP-activated protein kinase.

    DOI: 10.3164/jcbn.20-16

    PubMed

  • ビサクロンは脂質生成の阻害と脂肪分解の促進により肝臓への脂肪蓄積を抑制する(Bisacurone suppresses hepatic lipid accumulation through inhibiting lipogenesis and promoting lipolysis)

    Ashida Hitoshi, Tian Xiaokuo, Kitakaze Tomoya, Yamashita Yoko

    Journal of Clinical Biochemistry and Nutrition   67 ( 1 )   43 - 52   2020年07月( ISSN:0912-0009

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    化合物レベルのビサクロンによる肝臓の脂肪蓄積の減少作用を調べた。HepG2細胞を脂肪酸混合物、ビサクロン、クルクミンで処理した。5週齢雄性ICRマウス36匹を6群に割り付け、ビサクロン、クルクミン、陽性/陰性コントロールを7日間連続経口投与した。細胞内では、脂肪酸誘導性脂質蓄積がビサクロン処理で阻害された。ビサクロンは、脂肪酸の存在下AMPKαのリン酸化を有意に促進した。ビサクロンはACCαのリン酸化を増加させた。ビサクロンはPPARαとCPT1の発現を用量依存的に増加させた。マウスでは、ビサクロンの経口投与(10mg/kg体重)により肝臓の総脂質含量が減少した。ビサクロン投与によりトリグリセリド(1.0と10mg/kg体重投与群)と総コレステロール(全投与群)レベルが低下した。ビサクロン投与群(1.0と10mg/kg体重)では肝臓のAMPKα、ACCα、LKB1のリン酸化レベルが有意に上昇し、SREBP-1とChREBPの核内レベルが低下した。ビサクロンは肝臓のFASとC/EBPα発現レベルを有意に減少させた。ビサクロンは、AMPKα/ACCα経路のリン酸化調節だけでなく転写因子SREBP-1とChREBPの核内移行抑制により、肝臓の脂質生成を阻害していることが示唆された。ビサクロンは、肝臓の脂肪分解因子PPARαとCPT1の発現レベルを有意に上昇させた。

  • Prevention effect of quercetin and its glycosides on obesity and hyperglycemia through activating AMPKα in high-fat diet-fed ICR mice. 査読

    Hao Jiang, Yuko Horiuchi, Ken-Yu Hironao, Tomoya Kitakaze, Yoko Yamashita, Hitoshi Ashida

    Journal of clinical biochemistry and nutrition   67 ( 1 )   74 - 83   2020年07月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国内誌  

    Quercetin and its glycosides possess various health beneficial functions, but comparative study of them on energy metabolism in different tissues are not well studied. In this study, we investigated AMP-activated protein kinase regulated glucose metabolism in the skeletal muscle and lipid metabolism in the white adipose tissue and liver to compare the effectiveness of quercetin and its glycosides, namely isoquercitrin, rutin, and enzymatically modified isoquercitrin, in male ICR mice. The mice were fed a standard or high-fat diet supplemented with 0.1% quercetin and its glycosides for 13 weeks. Quercetin glycosides, but not quercetin, decreased body weight gain and fat accumulation in the mesenteric adipose tissue in high-fat groups. All compounds decreased high-fat diet-increased plasma glucose and insulin levels. Moreover, all compounds significantly increased AMP-activated protein kinase phosphorylation in either standard or high-fat diet-fed mice in all tissues tested. As its downstream events, all compounds induced glucose transporter 4 translocation in the muscle. In the white adipose tissue and liver, all compounds increased lipogenesis while decreased lipolysis. Moreover, all compounds increased browning markers and decreased differentiation markers in adipose tissue. Therefore, quercetin and its glycosides are promising food components for prevention of adiposity and hyperglycemia through modulating AMP-activated protein kinase-driven pathways.

    DOI: 10.3164/jcbn.20-47

    PubMed

  • Enzymatically synthesized glycogen protects inflammation induced by urban particulate matter in normal human epidermal keratinocytes. 査読

    Tomoya Kitakaze, Yasukiyo Yoshioka, Takashi Furuyashiki, Hitoshi Ashida

    Journal of clinical biochemistry and nutrition   67 ( 1 )   29 - 35   2020年07月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国内誌  

    Urban particulate matters (PM) exposure is significantly correlated with extrinsic skin aging signs and skin cancer incidence. PM contains polycyclic aromatic hydrocarbons, and they act as the agonists of aryl hydrocarbon receptor (AhR). Activation of AhR promotes generation of intracellular reactive oxygen species (ROS) and inflammation. Enzymatically synthesized glycogen (ESG), which is synthesized from starch, possesses various functions, such as anti-tumor, anti-obesity and antioxidant. However, the effects of ESG on PM-induced skin inflammation remain unclear. In this study, we investigated whether ESG has a protective effect on PM-induced oxidative stress and inflammation in human epidermal keratinocytes. ESG inhibited PM-induced expression of inflammatory cytokines IL6, TNFA and PTGS2. ESG also inhibited PM-induced phosphorylation of MAPKs and ROS accumulation. However, ESG had no effect on PM-induced expression of CYP1A1, one of the target proteins of AhR. On the other hand, ESG increased nuclear translocation of Nrf2 and expression of antioxidant proteins, HO-1 and NQO1. These results suggest that ESG suppressed PM-induced inflammation by decreasing ROS accumulation through the Nrf2 pathway.

    DOI: 10.3164/jcbn.20-43

    PubMed

  • Enzymatically synthesized glycogen prevents ultraviolet B-induced cell damage in normal human epidermal keratinocytes. 査読

    Yasukiyo Yoshioka, Tomoya Kitakaze, Takakazu Mitani, Takashi Furuyashiki, Hitoshi Ashida

    Journal of clinical biochemistry and nutrition   67 ( 1 )   36 - 42   2020年07月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国内誌  

    Enzymatically synthesized glycogen is a product from starch. Enzymatically synthesized glycogen has been reported to possess various health beneficial effects such as anti-oxidative and anti-inflammatory effects. In this study, we investigated the effect of enzymatically synthesized glycogen on ultraviolet B-induced oxidative stress and apoptosis in normal human epidermal keratinocytes. Treatment with enzymatically synthesized glycogen suppressed ultraviolet B-induced reactive oxygen species, caspase-3 activity, and DNA fragmentation in normal human epidermal keratinocytes. Furthermore, enzymatically synthesized glycogen increased in the expression level of heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, and NF-E2-related factor 2, a transcriptional factor for heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1. Although enzymatically synthesized glycogen did not increase in its mRNA expression level of NF-E2-related factor 2, enzymatically synthesized glycogen retained its protein degradation. Knockdown of heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 canceled enzymatically synthesized glycogen-suppressed reactive oxygen species accumulation in normal human epidermal keratinocytes. It is, therefore, concluded that enzymatically synthesized glycogen inhibited ultraviolet B-induced oxidative stress through increasing the expression level of heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 through the NF-E2-related factor 2 pathway in normal human epidermal keratinocytes.

    DOI: 10.3164/jcbn.20-44

    PubMed

  • 6-(Methylsulfinyl)hexyl isothiocyanate protects acetaldehyde-caused cytotoxicity through the induction of aldehyde dehydrogenase in hepatocytes. 査読

    Tomoya Kitakaze, Sihao Yuan, Masako Inoue, Yasukiyo Yoshioka, Yoko Yamashita, Hitoshi Ashida

    Archives of biochemistry and biophysics   686   108329 - 108329   2020年06月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    In the body, alcohol dehydrogenase rapidly converts ethanol to its toxic metabolite, acetaldehyde, which is further metabolized to non-toxic acetic acid by aldehyde dehydrogenase (ALDH). 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC), a major bioactive compound in Wasabi (Wasabia japonica) has various physiological effects such as anti-oxidative, anti-inflammatory and anti-cancer effects. However, the effect of 6-MSITC on alcohol metabolism has not been studied. In this study, we investigated the effects of 6-MSITC on hepatic ALDH activity and protein expression both in vitro and in vivo. 6-MSITC inhibited ethanol- and acetaldehyde-induced cytotoxicity. Treatment with 6-MSITC to HepG2 cells enhanced ALDH activity through the induction of mitochondrial ALDH2 expression, but not cytosolic ALDH1A1. Knockdown of Nrf2 canceled the 6-MSITC-induced ALDH2 expression, indicating that Nrf2 regulated ALDH2 expression. Moreover, 6-MSITC increased the nuclear translocation of Nrf2 and the expression levels of HO-1 and SOD2, Nrf2-regulated phase II drug-metabolizing enzymes. Oral administration of 6-MSITC increased the mitochondrial ALDH2 activity and its expression in the liver of C57BL/6J mice. These results suggested that 6-MSITC is possible to protect acetaldehyde toxicity in hepatocytes by induction of mitochondrial ALDH2 expression through Nrf2/ARE pathway.

    DOI: 10.1016/j.abb.2020.108329

    PubMed

  • 6-(Methylsulfinyl)hexyl isothiocyanate protects acetaldehyde-caused cytotoxicity through the induction of aldehyde dehydrogenase in hepatocytes

    Tomoya Kitakaze, Sihao Yuan, Masako Inoue, Yasukiyo Yoshioka, Yoko Yamashita, Hitoshi Ashida.

    Arch. Biochem. Biophys.   2020年06月

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    共著区分:共著  

  • Kaempferol modulates TCDD- and t-BHQ-induced drug-metabolizing enzymes and luteolin enhances this effect. 査読

    Tomoya Kitakaze, Atsushi Makiyama, Rika Nakai, Yuki Kimura, Hitoshi Ashida

    Food & function   11 ( 4 )   3668 - 3680   2020年04月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    The expression of drug-metabolizing enzymes is deeply involved in chemical-induced cancer progression and prevention. The aryl hydrocarbon receptor (AhR) induces phase I, and certain phase II drug-metabolizing enzymes after the binding of ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We have previously demonstrated that luteolin inhibited TCDD-induced AhR transformation, and modulated the expression of drug-metabolizing enzymes through not only the AhR, but also the nuclear factor-erythroid-2-related factor 2 (Nrf2). We have examined the effect of kaempferol on the expression of drug-metabolizing enzymes through modulation of the AhR- and Nrf2-pathways, and the effect of co-treatment with kaempferol and luteolin. Kaempferol dose-dependently inhibited not only the TCDD-induced expression of phase I and phase II drug-metabolizing enzymes, but also the tertiary butylhydroquinone (t-BHQ)-induced expression of phase II drug-metabolizing enzymes, by modulating the AhR- and Nrf2-pathways. Co-treatment with kaempferol and luteolin enhanced the inhibitory effect on the expression of drug-metabolizing enzymes, compared with either kaempferol or luteolin alone. Moreover, co-treatment with kaempferol and luteolin increased the cellular levels of kaempferol without affecting the levels of luteolin. An in vivo study was also performed and the results demonstrated that co-treatment with kaempferol and luteolin enhanced the inhibition of benzo[a]pyrene-induced drug-metabolizing enzymes compared with either kaempferol or luteolin alone, in the liver of ICR mice. These results suggest that luteolin promoted the incorporation of kaempferol into hepatocytes and enhanced the inhibitory effect of kaempferol on chemical-induced drug-metabolizing enzymes. Thus, luteolin enhances the kaempferol-inhibited expression of drug-metabolizing enzymes.

    DOI: 10.1039/c9fo02951f

    PubMed

  • Role of gut microbiota in sex- and diet-dependent metabolic disorders that lead to early mortality of androgen receptor-deficient male mice. 査読

    Naoki Harada, Kazuki Hanada, Yukari Minami, Tomoya Kitakaze, Yoshiyuki Ogata, Hayato Tokumoto, Takashi Sato, Shigeaki Kato, Hiroshi Inui, Ryoichi Yamaji

    American journal of physiology. Endocrinology and metabolism   318 ( 4 )   E525-E537   2020年04月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    The gut microbiota is involved in metabolic disorders induced by androgen deficiency after sexual maturation in males (late-onset hypogonadism). However, its role in the energy metabolism of congenital androgen deficiency (e.g., androgen-insensitive syndrome) remains elusive. Here, we examined the link between the gut microbiota and metabolic disease symptoms in androgen receptor knockout (ARKO) mouse by administering high-fat diet (HFD) and/or antibiotics. HFD-fed male, but not standard diet-fed male or HFD-fed female, ARKO mice exhibited increased feed efficiency, obesity with increased visceral adipocyte mass and hypertrophy, hepatic steatosis, glucose intolerance, insulin resistance, and loss of thigh muscle. In contrast, subcutaneous fat mass accumulated in ARKO mice irrespective of the diet and sex. Notably, all HFD-dependent metabolic disorders observed in ARKO males were abolished after antibiotics administration. The ratios of fecal weight-to-food weight and cecum weight-to-body weight were specifically reduced by ARKO in HFD-fed males. 16S rRNA sequencing of fecal microbiota from HFD-fed male mice revealed differences in microbiota composition between control and ARKO mice. Several genera or species (e.g., Turicibacter and Lactobacillus reuteri, respectively) were enriched in ARKO mice, and antibiotics treatment spoiled the changes. Furthermore, the life span of HFD-fed ARKO males was shorter than that of control mice, indicating that androgen deficiency causes metabolic dysfunctions leading to early death. These findings also suggest that AR signaling plays a role in the prevention of metabolic dysfunctions, presumably by influencing the gut microbiome, and improve our understanding of health consequences in subjects with hypogonadism and androgen insensitivity.

    DOI: 10.1152/ajpendo.00461.2019

    PubMed

  • Role of gut microbiota in sex- and diet-dependent metabolic disorders that lead to early mortality of androgen receptor-deficient male mice

    Naoki Harada, Kazuki Hanada, Yukari Minami, Tomoya Kitakaze, Yoshiyuki Ogata, Hayato Tokumoto, Takashi Sato, Shigeaki Kato, Hiroshi Inui, Ryoichi Yamaji.

    Am. J. Physiol. Endocrinol. Metab.   2020年04月

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    共著区分:共著  

  • Low dose of luteolin activates Nrf2 in the liver of mice at start of the active phase but not that of the inactive phase

    Tomoya Kitakaze, Atsushi Makiyama, Yoko Yamashita, Hitoshi Ashida.

    PLoS One   2020年04月

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    共著区分:共著  

  • Kaempferol modulates TCDD- and t-BHQ-induced drug-metabolizing enzymes and luteolin enhances this effect

    Tomoya Kitakaze, Atsushi Makiyama, Rika Nakai, Yuki Kimura, Hitoshi Ashida.

    Food Funct.   2020年04月

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    共著区分:共著  

  • Extracellular transglutaminase 2 induces myotube hypertrophy through G protein-coupled receptor 56

    Tomoya Kitakaze, Miki Yoshikawa, Yasuyuki Kobayashi, Naohiro Kimura, Naoki Goshima, Takahiro Ishikawa, Yoshiyuki Ogata, Yoko Yamashita, Hitoshi Ashida, Naoki Harada, Ryoichi Yamaji.

    Biochim. Biophys. Acta Mol. Cell Res.   2020年02月

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    共著区分:共著  

  • Extracellular transglutaminase 2 induces myotube hypertrophy through G protein-coupled receptor 56. 査読

    Tomoya Kitakaze, Miki Yoshikawa, Yasuyuki Kobayashi, Naohiro Kimura, Naoki Goshima, Takahiro Ishikawa, Yoshiyuki Ogata, Yoko Yamashita, Hitoshi Ashida, Naoki Harada, Ryoichi Yamaji

    Biochimica et biophysica acta. Molecular cell research   1867 ( 2 )   118563 - 118563   2020年02月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Skeletal muscle secretes biologically active proteins that contribute to muscle hypertrophy in response to either exercise or dietary intake. The identification of skeletal muscle-secreted proteins that induces hypertrophy can provide critical information regarding skeletal muscle health. Dietary provitamin A, β-carotene, induces hypertrophy of the soleus muscle in mice. Here, we hypothesized that skeletal muscle produces hypertrophy-inducible secretory proteins via dietary β-carotene. Knockdown of retinoic acid receptor (RAR) γ inhibited the β-carotene-induced increase soleus muscle mass in mice. Using RNA sequencing, bioinformatic analyses, and literature searching, we predicted transglutaminase 2 (TG2) to be an all-trans retinoic acid (ATRA)-induced secretory protein in cultured C2C12 myotubes. Tg2 mRNA expression increased in ATRA- or β-carotene-stimulated myotubes and in the soleus muscle of β-carotene-treated mice. Knockdown of RARγ inhibited β-carotene-increased mRNA expression of Tg2 in the soleus muscle. ATRA increased endogenous TG2 levels in conditioned medium from myotubes. Extracellular TG2 promoted the phosphorylation of Akt, mechanistic target of rapamycin (mTOR), and ribosomal p70 S6 kinase (p70S6K), and inhibitors of mTOR, phosphatidylinositol 3-kinase, and Src (rapamycin, LY294002, and Src I1, respectively) inhibited TG2-increased phosphorylation of mTOR and p70S6K. Furthermore, extracellular TG2 promoted protein synthesis and hypertrophy in myotubes. TG2 mutant lacking transglutaminase activity exerted the same effects as wild-type TG2. Knockdown of G protein-coupled receptor 56 (GPR56) inhibited the effects of TG2 on mTOR signaling, protein synthesis, and hypertrophy. These results indicated that TG2 expression was upregulated through ATRA-mediated RARγ and that extracellular TG2 induced myotube hypertrophy by activating mTOR signaling-mediated protein synthesis through GPR56, independent of transglutaminase activity.

    DOI: 10.1016/j.bbamcr.2019.118563

    PubMed

  • Low dose of luteolin activates Nrf2 in the liver of mice at start of the active phase but not that of the inactive phase. 査読

    Tomoya Kitakaze, Atsushi Makiyama, Yoko Yamashita, Hitoshi Ashida

    PloS one   15 ( 4 )   e0231403   2020年

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    A flavone luteolin has various health-promoting activities. Several studies reported that high dose of luteolin activates the Nrf2/ARE pathway in the liver. However, the effect of the low dose of luteolin that can be taken from a dietary meal on the Nrf2 activation remain unclear. It is expected that the flavonoid metabolism possesses a circadian rhythm, since nutritional metabolism processes daily cycle. In this study we investigated whether an administration affects the Nrf2 activation. ICR mice were orally administered 0.01-10 mg/kg body weight of luteolin once a day for 7 days at two time-points: at the start of active phase (ZT12) or at that of inactive phase (ZT0). Luteolin increased the nuclear translocation of Nrf2, resulting in the increases in its target gene products HO-1 and NQO1 at ZT12 but not at ZT0. The expression level of Nrf2 was lower at ZT12 than at ZT0 in the liver. We also found that the level of luteolin aglycon in the plasma is higher at ZT12 than at ZT0. These results suggest that the low dose of luteolin can activate Nrf2 pathway and the aglycon form of luteolin may mainly contribute to activate the Nrf2 pathway at ZT12 in the liver.

    DOI: 10.1371/journal.pone.0231403

    PubMed

  • A physiological concentration of luteolin induces phase II drug-metabolizing enzymes through the ERK1/2 signaling pathway in HepG2 cells. 査読

    Tomoya Kitakaze, Atsushi Makiyama, Yumi Samukawa, Songyan Jiang, Yoko Yamashita, Hitoshi Ashida

    Archives of biochemistry and biophysics   663   151 - 159   2019年03月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    The flavon luteolin has various health-promoting activities including cardiovascular protection, anti-inflammatory activity and anticancer activity. A serum concentration of about 100 nM luteolin is reached by dietary habit. However, little is known about the function of luteolin over its physiological concentration range. In this study, we investigated whether a physiological concentration of luteolin could activate nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated expression of phase II drug-metabolizing enzymes in human hepatoma HepG2 cells. Interestingly, less than 1 nM of luteolin could induce phase II drug-metabolizing enzymes, such as GSTs, HO-1, and NQO1. Both 1 and 100 nM luteolin increased expression and activity of ALDH2, which metabolized toxic acetaldehyde into nontoxic acetic acid. Luteolin increased nuclear accumulation of Nrf2 and enhanced the ARE-binding complex through increasing the stability of the Nrf2 protein. Luteolin increased phosphorylation of Nrf2 at Ser40, and MEK inhibitors (U0126 and PD98059) canceled luteolin-induced phosphorylation of Nrf2. Furthermore, luteolin increased modified Keap1. In conclusion, a physiological concentration of luteolin induces the expression of phase II drug-metabolizing enzymes by enhancement of Nrf2 nuclear accumulation through MEK1/2-ERK1/2-mediated phosphorylation of Nrf2, increasing Nrf2 stability and inducing a conformational change of Keap1.

    DOI: 10.1016/j.abb.2019.01.012

    PubMed

  • A physiological concentration of luteolin induces phase II drug-metabolizingenzymes through the ERK1/2 signaling pathway in HepG2 cells

    Tomoya Kitakaze, Atsushi Makiyama, Yumi Samukawa, Songyan Jiang, Yoko Yamashita, Hitoshi Ashida.

    Arch. Biochem. Biophys.   2019年03月

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    共著区分:共著  

  • 5-Hydroxy-7-methoxyflavone derivatives from Kaempferia parviflora induce skeletal muscle hypertrophy. 査読

    Shintaro Ono, Naoki Yoshida, Daisuke Maekawa, Tomoya Kitakaze, Yasuyuki Kobayashi, Takehiro Kitano, Takanori Fujita, Hirotaka Okuwa-Hayashi, Naoki Harada, Yoshihisa Nakano, Ryoichi Yamaji

    Food science & nutrition   7 ( 1 )   312 - 321   2019年01月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Skeletal muscle plays a critical role in locomotion and energy metabolism. Maintenance or enhancement of skeletal muscle mass contributes to the improvement of mobility and prevents the development of metabolic diseases. The extracts from Kaempferia parviflora rhizomes contain at least ten methoxyflavone derivatives that exhibit enhancing effects on ATP production and glucose uptake in skeletal muscle cells. In the present study, we investigated the effects of ten K. parviflora-derived methoxyflavone derivatives (six 5,7-dimethoxyflavone (DMF) derivatives and four 5-hydroxy-7-methoxyflavone (HMF) derivatives) on skeletal muscle hypertrophy. Murine C2C12 myotubes and senescence-accelerated mouse-prone 1 (SAMP1) mice treated with methoxyflavones were used as experimental models to determine the effects of HMF derivatives on myotube diameter and size and muscle mass. The four HMF derivatives, but not the six DMF derivatives, increased myotube diameter. The 5-hydroxyflavone, 7-methoxyflavone, and 5,7-dihydroxyflavone had no influence on myotube size, a result that differed from HMF. Dietary administration of the mixture composed of the four HMF derivatives resulted in increase in the soleus muscle size and mass in SAMP1 mice. HMF derivatives also promoted protein synthesis in myotubes, and treatment with the intracellular Ca2+ chelator BAPTA-AM, which depletes intracellular Ca2+ levels, inhibited this promotion. Furthermore, BAPTA-AM inhibited HMF-promoted protein synthesis even when myotubes were incubated in Ca2+-free medium. These results indicate that HMF derivatives induce myotube hypertrophy and that both the 5-hydroxyl group and the 7-methoxy group in the flavones are necessary for myotube hypertrophy. Furthermore, these results suggest that HMF-induced protein synthesis requires intracellular Ca2+, but not extracellular Ca2+.

    DOI: 10.1002/fsn3.891

    PubMed

  • 5-Hydroxy-7-methoxyflavone derivatives from Kaempferia parviflora induce skeletal muscle hypertrophy

    Shintaro Ono, Naoki Yoshida, Daisuke Maekawa, Tomoya Kitakaze, Yasuyuki Kobayashi, Takehiro Kitano, Takanori Fujita, Hirotaka Okuwa-Hayashi, Naoki Harada, Yoshihisa Nakano, Ryoichi Yamaji.

    Food Sci. Nutr.   2018年11月

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    共著区分:共著  

  • Lactoferrin promotes murine C2C12 myoblast proliferation and differentiation, and myotube hypertrophy

    Tomoya Kitakaze, Meiku Oshimo, Yasuyuki Kobayashi, Mizuyuki Ryu, Yasushi A. Suzuki, Hiroshi Inui, Naoki Harada, Ryoichi Yamaji.

    Mol. Med. Rep.   2018年04月

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    共著区分:共著  

  • Lactoferrin induces tropoelastin expression by activating the lipoprotein receptor-related protein 1-mediated phosphatidylinositol 3-kinase/Akt pathway in human dermal fibroblasts

    Mizuyuki Ryu, Asuka Nogami, Tomoya Kitakaze, Naok harada, Yasushi A. Suzuki, Ryoichi Yamaji.

    Cell Biol. Int.   2017年12月

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    共著区分:共著  

  • Daidzein down-regulates ubiquitin-specific protease 19 expression through estrogen receptor β and increases skeletal muscle mass in young female mice

    Masahiro Ogawa, Takehiro Kitano, Natsuha Kawata, Takashi Sugihira, Tomoya Kitakaze, Naoki Harada, Ryoichi Yamaji.

    J. Nutr. Biochem.   2017年11月

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    共著区分:共著  

  • The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy

    Tomoya Kitakaze, Tomotaka Sakamoto, Takehiro Kitano, Naoki Inoue, Fumihito Sugihara, Naoki Harada, Ryoichi Yamaji.

    Biochem. Biophys. Res. Commun.   2016年09月

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    共著区分:共著  

  • VHL-mediated degradation of HIF-2α regulates estrogen receptor α expression in normoxic breast cancer cells

    Yasuki Higashimura, Tomoya Kitakaze, Naoki Harada, Hiroshi Inui, Yoshihisa Nakano, Ryoichi Yamaji.

    FEBS Lett.   2016年08月

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    共著区分:共著  

  • Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice

    Naoki Harada, Ryo Hanaoka, Hiroko Horiuchi, Tomoya Kitakaze, Takakazu Mitani, Hiroshi Inui, Ryoichi Yamaji.

    Sci. Rep.   2016年03月

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    共著区分:共著  

  • β-Carotene increases muscle mass and hypertrophy in the soleus muscle in mice

    Tomoya Kitakaze, Naoki Harada, Hidetaka Imagita, Ryoichi Yamaji.

    J. Nutr. Sci. Vitaminol. (Tokyo)   2016年02月

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    共著区分:共著  

  • Female-specific regulation of skeletal muscle mass by USP19 in young mice

    Masahiro Ogawa, Tomoya Kitakaze, Naoki Harada and Ryoichi Yamaji.

    J. Endocrinol.   2015年06月

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    共著区分:共著  

  • The preventive effect of β-carotene on denervation-induced soleus muscle atrophy in mice

    Masahiro Ogawa, Yoshihiro Kariya, Tomoya Kitakaze, Ryoichi Yamaji, Naoki Harada, Tatsuji Sakamoto, Keisuke Hosotani, Yoshihisa Nakano, Hiroshi Inui.

    Br. J. Nutr.   2013年04月

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    共著区分:共著  

▼全件表示

書籍等出版物

  • ビタミン・バイオファクター総合辞典 3.1.6 トピックス(カロテンと骨格筋と脂肪組織)

    北風智也、山地亮一( 担当: 共著)

    朝倉書店  2021年07月 

  • 代謝センシング~健康、食、美容、薬そして脳の代謝を知る~第11章 カロテンとその代謝物による骨格筋へのヘルスベネフィット

    北風智也、原田直樹、山地亮一( 担当: 共著)

    シーエムシー出版  2019年09月 

MISC(その他記事)

  • 全トランス型レチノイン酸に依存したLGR6の筋分化における一過性発現は筋芽細胞の分化と融合を調節する

    北風智也、辰巳理奈、山口真由、中辻あいの、原田直樹、山地亮一

    ビタミン   98   70 - 73   2023年11月

  • 網膜に集まるカロテノイド

    北風智也

    生物工学会誌   101   552 - 552   2023年10月

  • 【からだが"ととのう"睡眠と時間栄養】フラボノイドの概日リズム調節作用

    北風 智也

    FOOD Style 21   27 ( 9 )   73 - 77   2023年09月( ISSN:1343-9502

  • 食品因子の薬物代謝系を介した生体防御機能に関する研究(令和4年度日本栄養・食糧学会奨励賞受賞)

    北風 智也

    日本栄養・食糧学会誌   75 ( 6 )   291 - 296   2022年12月( ISSN:0287-3516

     詳細を見る

    生体外異物であるダイオキシン類による毒性はアリール炭化水素受容体(AhR)を介した作用であるため,AhRの活性化を抑制することが毒性の緩和につながる。ダイオキシン類の毒性の緩和は転写因子nuclear factor-erythroid 2-related factor 2(Nrf2)を介した薬物代謝第II相酵素の誘導も有効である。Nrf2の活性化はダイオキシン類の曝露以外の環境ストレスに対する生体防御機能も高める。そのため,AhRを抑制しNrf2を活性化する食品因子の探索を行ってきた。筆者はこれまでに,フラボノイドであるルテオリンとケンフェロールの共作用がAhRの活性抑制効果を増強すること,日常的な食事から摂取可能な量のルテオリンがNrf2を活性化することを明らかにした。また,AhRの活性化が引き起こす肝臓への脂肪蓄積が,概日リズムの乱れに起因することと,ルテオリンとケンフェロールによる抑制効果を見出した。これらのことから,ルテオリンとケンフェロールは薬物代謝系を介した生体外異物に対する生体防御機能に関して,有効性が明らかとなった。(著者抄録)

  • 骨格筋における異所性脂肪蓄積に対するレチノイン酸受容体アゴニストの抑制効果

    辰巳 理奈, 北風 智也, 原田 直樹, 山地 亮一

    ビタミン   96 ( 5-6 )   239 - 243   2022年06月( ISSN:0006-386X

講演・口頭発表等

▼全件表示

科研費獲得実績

  • ビタミンAに応答するマイオカインの探索と機能解明

    若手研究  2024年

  • ビタミンAに応答するマイオカインの探索と機能解明

    若手研究  2023年

  • 生体リズムにおけるビタミンAの機能性解析

    研究活動スタート支援  2021年

  • 運動後の骨格筋におけるビタミンAの機能性に関する研究

    若手研究  2021年

担当授業科目

  • 生命機能化学概論

    2024年度   週間授業   大学

  • 生体成分実験

    2021年度   実習  

  • 生命機能化学概論

    2021年度    

  • 生体成分実験

    2021年度   実習  

  • 生命機能化学概論

    2021年度