کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3315206 1211248 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Preventing hypoxia/reoxygenation damage to hepatocytes by p66shc ablation: Up-regulation of anti-oxidant and anti-apoptotic proteins
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Preventing hypoxia/reoxygenation damage to hepatocytes by p66shc ablation: Up-regulation of anti-oxidant and anti-apoptotic proteins
چکیده انگلیسی

Background/AimsIschemia/reperfusion damage to the liver remains a serious concern in many clinical situations. Major mechanisms for this certainly include oxidative stress.MethodsThe effects of ablating the p66 isoform of ShcA (p66shc) on hypoxia/reoxygenation (H/R)-induced oxidative stress and cell injury in hepatocytes were investigated.ResultsImmediately after reoxygenation, AML12 cells were clearly under oxidative stress; many cells underwent apoptosis. However, knockdown of p66shc by specific RNAi markedly decreased cellular oxidative stress and H/R-induced apoptosis, as well as conferring resistance to H2O2 insult. These data suggest that prevention of apoptosis conferred by ablation of p66shc results from changed ROS-scavenging, but not inhibition of ROS generation. These data were also confirmed in fibroblasts from p66shc knockout mice. Anti-oxidant molecules, such as MnSOD and Ref-1 and the anti-apoptotic molecule Bcl-xL were up-regulated, and pro-apoptotic FLICE was down-regulated, by ablation of p66shc. Interestingly, catalase expression was not affected in p66shc-knockdown-AML12 cells although it is a major target in other cell types.ConclusionsOur findings suggest that in hepatocytes, ablation of p66shc is cytoprotective against H/R-induced oxidative stress, with MnSOD and Ref-1 playing critical roles, and with up-regulation of Bcl-xL and down-regulation of FLICE contributing jointly to preventing cells from undergoing oxidant-induced apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 48, Issue 3, March 2008, Pages 422–432
نویسندگان
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