کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1929199 1050448 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Eicosapentaenoic acid attenuates statin-induced ER stress and toxicity in myoblast
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Eicosapentaenoic acid attenuates statin-induced ER stress and toxicity in myoblast
چکیده انگلیسی

We previously reported that eicosapentaenoic acid (EPA) improved statin-induced rhabdomyolysis in rats (Naba et al. [6]). In this study, we report for the first time direct improvement by EPA of statin-induced toxicity in cultured myoblasts and the mechanistic involvement of endoplasmic reticulum (ER) stress. Differentiated rhabdomyosarcoma cells (RD cells) were treated with statins and EPA for 1–4 days. Statins induced various toxic changes in RD cells, and EPA attenuated all of these changes. Interestingly, statins increased mRNA expression of ER stress markers (XBP-1 and CHOP) and EPA attenuated both. Further, in a statin-induced rat model of rhabdomyolysis, these markers in skeletal muscle were significantly correlated with plasma CPK activity. In RD cells, statins also increased p-c-Jun protein content and caspase-3/7 activity, while 4-PBA, an ER stress attenuator, PPAR-δ agonist, and EPA attenuated them. These findings suggest that EPA attenuates statin-induced ER stress, JNK activation and toxicity in cultured myoblast cells, and that PPAR-δ may mechanically involved in the effects of EPA.


► We previously reported that EPA improved statin-induced rhabdomyolysis in rats.
► This time we show that EPA inhibits statin-attenuated toxicity in cultured myoblasts.
► We firstly report that statin induces ER stress, and EPA attenuates it in myoblasts.
► ER stress markers in muscles of rat rhabdomyolysis models correlated with plasma CPK.
► JNK and PPAR-δ may play some roles in the mechanism responsible for this phenomenon.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 424, Issue 2, 27 July 2012, Pages 301–307
نویسندگان
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