کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474404 | 1550425 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of the mevalonate pathway ameliorates anoxia-induced down-regulation of FKBP12.6 and intracellular calcium handling dysfunction in H9c2 cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
RyRPLBGGPPHMG-CoApKaRho-kinaseRT-PCRGAPDHDMEMFPPFKBP3-hydroxy-3-methylglutaryl-coenzyme A - 3-هیدروکسی-3-methylglutaryl-coenzyme ADMSO - DMSOSmall GTPase - GTPase کوچکDulbecco's modified Eagle's medium - Medal of Eagle اصلاح شده DulbeccoMTT - MTTCalcium handling - دست زدن به کلسیمDimethylsulfoxide - دیمتیل سولفواکسیدSarcoplasmic reticulum - رتیکولوم سارکوپلاسمیکfarnesyl pyrophosphate - فارسیل پیرو فسفاتphospholamban - فسفولامبنSERCA - قلبMevalonate pathway - مسیر مولکولیreverse transcription polymerase chain reaction - واکنش زنجیره ای پلیمراز رونویسی معکوسFK506-binding protein - پروتئین اتصال دهنده FK506cAMP-dependent protein kinase A - پروتئین کیناز A وابسته به cAMPgeranylgeranyl pyrophosphate - ژرینیل گرانیل پیرو فسفاتGlyceraldehyde phosphate dehydrogenase - گلیسرالیدید فسفات دهیدروژنازRyanodine receptor - گیرنده رایانودینRyanodine receptor 2 - گیرنده رایانودین 2Rock - یا راک
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Statins have beneficial pleiotropic effects beyond lipid lowering on the cardiovascular system. These cardio-protective effects are mediated through inhibition of the intracellular mevalonate pathway, by decreasing isoprenoid intermediate synthesis and the subsequent post-translational modification of small GTPases, such as Ras, Rho, and Rac. Impaired intracellular calcium handling is considered an important pathophysiologic mechanism responsible for cardiac dysfunction. Our study aimed at investigating the influence of mevalonate pathway, including its downstream small GTPases (Ras, RhoA, and Rac1) on anoxia-mediated alterations of calcium handling in H9c2 cardiomyocytes. Cultured H9c2 cardiomyocytes were exposed to acute anoxia after pretreatment with different drugs that specifically antagonize five key components in the mevalonate pathway, including 3-hydroxy-3-methylglutaryl-CoA reductase, farnesyl pyrophosphate synthase, Rho-kinase, Rac1 and Ras farnesyltransferase. Thereafter, we evaluated the effects of the mevalonate pathway on anoxia-induced cell death, expression of the sarcoplasmic reticulum calcium release channel (ryanodine receptor 2) and its regulator FK506-binding protein 12.6, as well as functional calcium release from intracellular calcium stores. Our experiments confirmed the role of prenylated proteins in regulating cardiomyocyte dysfunction, especially via RhoA- and Ras-related signaling pathways. Furthermore, our data demonstrated that inhibition of the mevalonate pathway could ameliorate anoxia-mediated calcium handling dysfunction with the up-regulated expression of FK506-binding protein 12.6 and consequently provided evidence for FK506-binding protein 12.6 as a “stabilizer” of ryanodine receptor 2.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 80, March 2015, Pages 166-174
Journal: Journal of Molecular and Cellular Cardiology - Volume 80, March 2015, Pages 166-174
نویسندگان
Ying Yang, Xue Lu, Xiqing Rong, Wenbing Jiang, Dongwu Lai, Yan Ma, Ke Zhou, Guosheng Fu, Shiming Xu,