کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6108038 1211183 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Variable activation of phosphoinositide 3-kinase influences the response of liver grafts to ischemic preconditioning
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Variable activation of phosphoinositide 3-kinase influences the response of liver grafts to ischemic preconditioning
چکیده انگلیسی

Background/AimsThe efficacy of ischemic preconditioning (IPC) in preventing reperfusion injury in human liver transplants is still questioned. Phosphoinositide-3-kinase (PI3K) is essential for IPC development in rodent livers. This work investigates whether PI3K-dependent signals might account for the inconsistent responses to IPC of transplanted human livers.MethodsForty livers from deceased donors were randomized to receive or not IPC before recovery. PI3K activation was evaluated in biopsies obtained immediately before IPC and 2 h after reperfusion by measuring the phosphorylation of the PI3K downstream kinase PKB/Akt and the levels of the PI3K antagonist phosphatase tensin-homologue deleted from chromosome 10 (PTEN).ResultsIPC increased PKB/Akt phosphorylation (p = 0.01) and decreased PTEN levels (p = 0.03) in grafts, but did not significantly ameliorate post-transplant reperfusion injury. By calculating T2h/T0 PKB/Akt phosphorylation ratios, 10/19 (53%) of the preconditioned grafts had ratios above the control threshold (IPC-responsive), while the remaining nine grafts showed ratios comparable to controls (IPC-non-responsive). T2h/T0 PTEN ratios were also decreased (p ⩽ 0.03) only in IPC-responsive grafts. The patients receiving IPC-responsive organs had ameliorated (p ⩽ 0.05) post-transplant aminotransferase and bilirubin levels, while prothrombin activity was unchanged.ConclusionsImpaired PI3K signaling might account for the variability in the responses to IPC of human grafts from deceased donors.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 50, Issue 5, May 2009, Pages 937-947
نویسندگان
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