کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2191466 1097862 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oxidative injury induces selective rather than global inhibition of proteasomal activity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Oxidative injury induces selective rather than global inhibition of proteasomal activity
چکیده انگلیسی

Oxidative injury has been found to be associated with proteasomal inactivity. In this study, the extent of oxidative damage and its effects on proteasomal function has been critically assessed. Left anterior descending coronary artery was occluded (ischemia) and reperfused with or without preconditioning in male Sprague–Dawley rats. For further validation, H9c2 cardiac myoblasts cultures were used. We demonstrate that ischemia–reperfusion causes extensive endoplasmic reticulum stress as evident from the degradation of GRP78 transcript followed by its rapid induction. Western blot analysis and immunohistochemistry showed that increasing duration of ischemia and reperfusion causes accumulation of phosphorylated IκB (p-IκB), thereby suggesting proteasomal inactivity. However, similar analysis for Nrf2, a key mediator of antioxidant defense, showed sustained activation, suggesting intact proteasomal function. Preconditioning of the myocardium preserves the degradation of p-IκB, suggesting effective functioning of proteasome after preconditioning. Further analysis with specific proteosomal inhibitors like epoxomicin (100 nM, inhibits chymotrypsin-like activities of proteasomes) and lactacystin (2 μM, inhibits chymotrypsin as well as some trypsin-like activities of proteasomes) suggests that degradation of p-IκB and Keap-1 in the proteasome occurs by independent mechanisms. This study gives further insight into interrelationship between oxidative injury and catalytic function of the proteasome in heart, where oxidative injury causes selective rather than global inhibition of proteasome.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 44, Issue 2, February 2008, Pages 419–428
نویسندگان
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