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dc.contributor.authorAhmed, Munzir M. E.
dc.contributor.authorWang, Tao
dc.contributor.authorLuo, Yu
dc.contributor.authorYe, Shuilong
dc.contributor.authorWu, Qiao
dc.contributor.author吴乔
dc.contributor.authorGuo, Zongsheng
dc.contributor.authorRoebuck, Bill D.
dc.contributor.authorSutter, Thomas R.
dc.contributor.authorYang, James Y.
dc.date.accessioned2012-03-22T07:06:11Z
dc.date.available2012-03-22T07:06:11Z
dc.date.issued2011-09-06
dc.identifier.citationHepatology. 2011 Oct;54(4):1322-32. doi: 10.1002/hep.24493zh_CN
dc.identifier.issn0270-9139
dc.identifier.urihttp://dx.doi.org/doi:10.1002/hep.24493
dc.identifier.uriWOS:000295577200024
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/11838
dc.description.abstractesponsive transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a protein highly responsive to acetaminophen (APAP) or its intermediate metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). This study was, therefore, carried out to investigate whether Akr7a is involved in the protection against APAP-induced oxidative stress and hepatotoxicity. We found that in response to APAP or NAPQI exposure, Akr7a3 mRNA and protein were significantly up-regulated in vitro in human HepG2 and LO2 cells. Similarly, strong induction was observed for Akr7a5 in mouse AML12 hepatocytes exposed to APAP. In vivo in wild-type rats, significant up-regulation of hepatic AKR7A1 protein was observed after administration of APAP. On the other hand, depletion of Nrf2 reduced the expression of Akr7a3, suggesting that Nrf2, indeed, contributes significantly to the induction of Akr7a. Moreover, loss of cell viability in Nrf2-depleted cells was significantly rescued by coexpression of AKR7A3. Furthermore, increased AKR7A3 in HepG2 cells was associated with the up-regulation of oxidative stress-related enzymes to enhance cellular antioxidant defense, which appeared to contribute significantly to protection against APAP-induced toxicity. In a line of transgenic rats overexpressing AKR7A1, increased AKR7A1 stimulated the expression of Nrf2 and other Nrf2-regulated genes, but did not better protect rats from APAP insults. In contrast, depletion of Akr7a5 in vitro in cultured AML12 cells or depletion of Akr7a1 in vivo in rat liver greatly increased APAP-induced hepatotoxicity. Conclusion: AKR7A proteins are significantly up-regulated in response to APAP/NAPQI exposure to contribute significantly to protection against APAP-induced hepatotoxicity. AKR7A mediates this protection, in part, through enhancing hepatocellular antioxidant defense. (HEPATOLOGY 2011;54:1322-1332)zh_CN
dc.description.sponsorshipNational Science Foundation of China[30970649]; 973 Program of China[2009CB941601]; Fujian Provincial Department of Science and Technology[2010L0002]; Science Planning Program of Fujian Province[2010J1008]zh_CN
dc.language.isoenzh_CN
dc.publisherWILEY-BLACKWELLzh_CN
dc.titleAldo-Keto Reductase-7A Protects Liver Cells and Tissues From Acetaminophen-Induced Oxidative Stress and Hepatotoxicityzh_CN
dc.typeArticlezh_CN


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