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著作: [冨永 辰也]/Dutta Rajesh K/Joladarashi Darukeshwara/[土井 俊夫]/Reddy Janardan K/Kanwar Yashpal S/Transcriptional and Translational Modulation of myo-Inositol Oxygenase (Miox) by Fatty Acids: IMPLICATIONS IN RENAL TUBULAR INJURY INDUCED IN OBESITY AND DIABETES./[The Journal of Biological Chemistry]

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EID
311048
EOID
816521
Map
0
LastModified
2016年4月20日(水) 14:56:07
Operator
三好 小文
Avail
TRUE
Censor
0
Owner
冨永 辰也
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨 研究
共著種別 推奨 国際共著(徳島大学内研究者と国外研究機関所属研究者との共同研究)
学究種別 推奨
組織 推奨
著者 必須
  1. 冨永 辰也([徳島大学.大学院医歯薬学研究部.保健学域.保健科学部門.医用検査学系.細胞・免疫解析学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Dutta Rajesh K
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Joladarashi Darukeshwara
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. 土井 俊夫
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Reddy Janardan K
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Kanwar Yashpal S
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Transcriptional and Translational Modulation of myo-Inositol Oxygenase (Miox) by Fatty Acids: IMPLICATIONS IN RENAL TUBULAR INJURY INDUCED IN OBESITY AND DIABETES.

副題 任意
要約 任意

(英) The kidney is one of the target organs for various metabolic diseases, including diabetes, metabolic syndrome, and obesity. Most of the metabolic studies underscore glomerular pathobiology, although the tubulo-interstitial compartment has been underemphasized. This study highlights mechanisms concerning the pathobiology of tubular injury in the context of myo-inositol oxygenase (Miox), a tubular enzyme. The kidneys of mice fed a high fat diet (HFD) had increased Miox expression and activity, and the latter was related to phosphorylation of serine/threonine residues. Also, expression of sterol regulatory element-binding protein1 (Srebp1) and markers of cellular/nuclear damage was increased along with accentuated apoptosis and loss of tubular brush border. Similar results were observed in cells treated with palmitate/BSA. Multiple sterol-response elements and E-box motifs were found in the miox promoter, and its activity was modulated by palmitate/BSA. Electrophoretic mobility and ChIP assays confirmed binding of Srebp to consensus sequences of the miox promoter. Exposure of palmitate/BSA-treated cells to rapamycin normalized Miox expression and prevented Srebp1 nuclear translocation. In addition, rapamycin treatment reduced p53 expression and apoptosis. Like rapamycin, srebp siRNA reduced Miox expression. Increased expression of Miox was associated with the generation of reactive oxygen species (ROS) in kidney tubules of mice fed an HFD and cell exposed to palmitate/BSA. Both miox and srebp1 siRNAs reduced generation of ROS. Collectively, these findings suggest that HFD or fatty acids modulate transcriptional, translational, and post-translational regulation of Miox expression/activity and underscore Miox being a novel target of the transcription factor Srebp1. Conceivably, activation of the mTORC1/Srebp1/Miox pathway leads to the generation of ROS culminating into tubulo-interstitial injury in states of obesity.

キーワード 推奨
発行所 推奨
誌名 必須 The Journal of Biological Chemistry([The American Society for Biochemistry and Molecular Biology])
(pISSN: 0021-9258, eISSN: 1083-351X)
ISSN 任意 1083-351X
ISSN: 0021-9258 (pISSN: 0021-9258, eISSN: 1083-351X)
Title: The Journal of biological chemistry
Title(ISO): J Biol Chem
Publisher: American Society for Biochemistry and Molecular Biology
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 291
必須 3
必須 1348 1367
都市 任意
年月日 必須 2015年 11月 17日
URL 任意
DOI 任意 10.1074/jbc.M115.698191    (→Scopusで検索)
PMID 任意 26578517    (→Scopusで検索)
CRID 任意
WOS 任意 000368068300028
Scopus 任意 2-s2.0-84954486114
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) PublicationType: Journal Article