کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259821 | 1534647 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2Â + leak in cardiomyocytes: Role of adenine nucleotide translocase
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کلمات کلیدی
ANTAp5AAK2IK1FKBP12.6MPTPoLCLCACNACDPIN-acetylcysteine - N-استیل سیستئینNOx - NOXBongkrekic acid - اسید بونکروکیکFatty acid - اسید چربmitochondrial permeability transition pore - انتقال نفوذی میتوکندری منفی استNADPH oxidase - اکسیداز NADPH CSA - ایالات مؤتلفهٔ آمریکاadenine nucleotide translocase - ترانسکوز نوکلئوتید آدنینIntravenous - داخل وریدیDiphenyleneiodonium - دیفنیلن اندونیمCyclosporine A - سیکلوسپورینACarnitine - کارنیتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2Â + leak in cardiomyocytes: Role of adenine nucleotide translocase Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2Â + leak in cardiomyocytes: Role of adenine nucleotide translocase](/preview/png/8259821.png)
چکیده انگلیسی
Long chain fatty acids bind to carnitine and form long chain acyl carnitine (LCAC), to enter into the mitochondria. They are oxidized in the mitochondrial matrix. LCAC accumulates rapidly under metabolic disorders, such as acute cardiac ischemia, chronic heart failure or diabetic cardiomyopathy. LCAC accumulation is associated with severe cardiac arrhythmia including ventricular tachycardia or fibrillation. We thus hypothesized that palmitoyl-carnitine (PC), alters mitochondrial function leading to Ca2 + dependent-arrhythmia. In isolated cardiac mitochondria from C57Bl/6 mice, application of 10 μM PC decreased adenine nucleotide translocase (ANT) activity without affecting mitochondrial permeability transition pore (mPTP) opening. Mitochondrial reactive oxygen species (ROS) production, measured with MitoSOX Red dye in isolated ventricular cardiomyocytes, increased significantly under PC application. Inhibition of ANT by bongkrekic acid (20 μM) prevented PC-induced mitochondrial ROS production. In addition, PC increased type 2 ryanodine receptor (RyR2) oxidation, S-nitrosylation and dissociation of FKBP12.6 from RyR2, and therefore increased sarcoplasmic reticulum (SR) Ca2 + leak. ANT inhibition or anti-oxidant strategy (N-acetylcysteine) prevented SR Ca2 + leak, FKBP12.6 depletion and RyR2 oxidation/S-nitrosylation induced by PC. Finally, both bongkrekic acid and NAC significantly reduced spontaneous Ca2 + wave occurrences under PC. Altogether, these results suggest that an elevation of PC disturbs ANT activity and alters Ca2 + handling in a ROS-dependent pathway, demonstrating a new pathway whereby altered FA metabolism may contribute to the development of ventricular arrhythmia in pathophysiological conditions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 5, May 2015, Pages 749-758
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 5, May 2015, Pages 749-758
نویسندگان
J. Roussel, J. Thireau, C. Brenner, N. Saint, V. Scheuermann, A. Lacampagne, J.-Y. Le Guennec, J. Fauconnier,