کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2554576 1124976 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clofibrate-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Clofibrate-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation
چکیده انگلیسی

The mechanism of fibrate-induced myopathy was investigated in this report. When clofibrate (30 to 300 μM) was applied to L6 rat skeletal myoblasts, dose-dependently apoptosis was observed within 24 h. In the apoptotic myoblasts, a caspase-12 cleavage was observed at 2 h and with following caspases-9 and -3-related cascade activation. In contrast, the neutral protease calpain, that is a key enzyme in ER stress-related apoptosis via caspase-12 activation, was significantly decreased during apoptosis. Next, the authors evaluated a role of calcium-dependent signal(s). When clofibrate was added into medium, cytosolic calcium concentration was rapidly and persistently increased. On the other hand, an addition of 10 mM EGTA depressed sustained calcium phase, and concurrent myoblasts apoptosis was completely inhibited. Taken together, our findings indicate that the clofibrate-induced myopathy is triggered by Ca2+ influx, then activated cytosolic caspase-12 through calpain-independent cascade, and consequently caused apoptotic DNA fragmentation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 78, Issue 16, 13 March 2006, Pages 1892–1899
نویسندگان
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