کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
1904444 1534628 2016 11 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Disruption of calpain reduces lipotoxicity-induced cardiac injury by preventing endoplasmic reticulum stress
ترجمه فارسی عنوان
اختلال در کالپین آسیب قلبی ناشی از lipotoxicity برای جلوگیری از استرس شبکه آندوپلاسمی را کاهش می دهد
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کلمات کلیدی
پپتید ناتریورتیک دهلیزی، فعال شدن فاکتور رونویسی 4؛ زنجیره سنگین میوزین بتا؛ زیر واحد نظارتی کوچک کالپین؛ ریز ریز کردن، پروتئین همولوگ؛ شبکه آندوپلاسمی؛ چاپرون گلوکز تنظیم پروتئین7
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی


• Disruption of calpain prevents cardiac lipotoxic injury.
• Calpain induces ER stress and inflammatory response in cardiac lipotoxicity.
• Inhibition of ER stress prevents lipotoxicity-induced apoptosis in cardiomyocytes.
• ER stress contributes to cardiac inflammatory response in cardiac lipotoxicity.

Diabetes and obesity are prevalent in westernized countries. In both conditions, excessive fatty acid uptake by cardiomyocytes induces cardiac lipotoxicity, an important mechanism contributing to diabetic cardiomyopathy. This study investigated the effect of calpain disruption on cardiac lipotoxicity. Cardiac-specific capns1 knockout mice and their wild-type littermates (male, age of 4 weeks) were fed a high fat diet (HFD) or normal diet for 20 weeks. HFD increased body weight, altered blood lipid profiles and impaired glucose tolerance comparably in both capns1 knockout mice and their wild-type littermates. Calpain activity, cardiomyocyte cross-sectional areas, collagen deposition and triglyceride were significantly increased in HFD-fed mouse hearts, and these were accompanied by myocardial dysfunction and up-regulation of hypertrophic and fibrotic collagen genes as well as pro-inflammatory cytokines. These effects of HFD were attenuated by disruption of calpain in capns1 knockout mice. Mechanistically, deletion of capns1 in HFD-fed mouse hearts and disruption of calpain with calpain inhibitor-III, silencing of capn1, or deletion of capns1 in palmitate-stimulated cardiomyocytes prevented endoplasmic reticulum stress, apoptosis, cleavage of caspase-12 and junctophilin-2, and pro-inflammatory cytokine expression. Pharmacological inhibition of endoplasmic reticulum stress diminished palmitate-induced apoptosis and pro-inflammatory cytokine expression in cardiomyocytes. In summary, disruption of calpain prevents lipotoxicity-induced apoptosis in cardiomyocytes and cardiac injury in mice fed a HFD. The role of calpain is mediated, at least partially, through endoplasmic reticulum stress. Thus, calpain/endoplasmic reticulum stress may represent a new mechanism and potential therapeutic targets for cardiac lipotoxicity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 11, November 2016, Pages 2023–2033
نویسندگان
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