| Eicosapentaenoic Acid Attenuates Statin-Induced ER stress and Toxicity in Myoblast. | |
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MedLine Citation:
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PMID: 22749998 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We previously reported that eicosapentaenoic acid (EPA) improved statin-induced rhabdomyolysis in rats [Naba et al., 2006]. 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. |
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Authors:
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Masahiko Ohta; Hiroyuki Kawano; Tatsuto Notsu; Hiroyasu Naba; Kazunori Imada |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-27 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: - ISSN: 1090-2104 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-7-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
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Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., 722 Uenohara, Jimba, Gotemba 412-8524, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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