TRPV4 activation of endothelial nitric oxide synthase resists nonalcoholic fatty liver disease by blocking CYP2E1-mediated redox toxicity

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• 作者：Ratanesh K. Seth^a ; Suvarthi Das^a ; Diptadip Dattaroy^a ; Varun Chandrashekaran^a ; Firas Alhasson^a ; Gregory Michelotti^b ; Mitzi Nagarkatti^c ; Prakash Nagarkatti^c ; Anna Mae Diehl^d ; P. Darwin Bell^e ; Wolfgang Liedtke^f ; ^{liedt001@duke.edu} ; Saurabh Chatterjee^a ; ^{schatt@mailbox.sc.edu}
• 关键词：Oxidative stress ; Lipid peroxidation ; Hydroxynonenal ; Liver ; Cation channel mechanosensor
• 刊名：Free Radical Biology and Medicine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：102
• 期：Complete
• 页码：260-273
• 全文大小：3555 K
• 卷排序：102

文摘

TRPV4 loss of function leads to uninterrupted CYP2E1 activity and protein levels. Blocking CYP2E1-induced redox toxicity improves outcome in NAFLD pathology. TRPV4 blocks CYP2E1 activity by activating NOS3 and NO release. Mechanistically, Kupffer cell induced NO blocks CYP2E1 in a paracrine manner. TRPV4-CYP2E1 axis is a novel pathway in NAFLD pathology.