کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259815 | 1534647 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial dysfunction and epigenetic modifications
ترجمه فارسی عنوان
ضعف عضلانی اسکلتی مرتبط با هیپر هوموسیستئینمی شامل اختلال عملکرد میتوکندریایی و تغییرات اپی ژنتیکی
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کلمات کلیدی
MM-CKCOX-IVBetaine-homocysteine S-methyltransferaseHHcyNRFMIRMFN2BHMTCBSPGC-1αNRF-1DnmtHcy5-mC - 5 سانتیمترDNA methyltransferase - DNA متیل ترانسفرازmtTFA - MTTFEpigenetics - اپی ژنتیکDystrophin - دیستروفینCitrate synthase - سیترات سیتواستاتcytochrome c oxidase subunit IV - سیتوکروم C اکسیداز Subunit IVcystathionine β-synthase - سیستاتیونین β-سنتازNuclear respiratory factor - عامل تنفسی هسته ایmitochondrial transcription factor A - عامل رونویسی میتوکندری Alactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH MicroRNA - میکرو RNA homocysteine - هوموسیستئینHyperhomocysteinemia - هیپر هوموسایستنمیexercise - ورزش
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
چکیده انگلیسی
HHcy has been implicated in elderly frailty, but the underlying mechanisms are poorly understood. Using C57 and CBSÂ +/â mice and C2C12 cell line, we investigated mechanisms behind HHcy induced skeletal muscle weakness and fatigability. Possible alterations in metabolic capacity (levels of LDH, CS, MM-CK and COX-IV), in structural proteins (levels of dystrophin) and in mitochondrial function (ATP production) were examined. An exercise regimen was employed to reverse HHcy induced changes. CBSÂ +/â mice exhibited more fatigability, and generated less contraction force. No significant changes in muscle morphology were observed. However, there is a corresponding reduction in large muscle fiber number in CBSÂ +/â mice. Excess fatigability was not due to changes in key enzymes involved in metabolism, but was due to reduced ATP levels. A marginal reduction in dystrophin levels along with a decrease in mitochondrial transcription factor A (mtTFA) were observed. There was also an increase in the mir-31, and mir-494 quantities that were implicated in dystrophin and mtTFA regulation respectively. The molecular changes elevated during HHcy, with the exception of dystrophin levels, were reversed after exercise. In addition, the amount of NRF-1, one of the transcriptional regulators of mtTFA, was significantly decreased. Furthermore, there was enhancement in mir-494 levels and a concomitant decline in mtTFA protein quantity in homocysteine treated cells. These changes in C2C12 cells were also accompanied by an increase in DNMT3a and DNMT3b proteins and global DNA methylation levels. Together, these results suggest that HHcy plays a causal role in enhanced fatigability through mitochondrial dysfunction which involves epigenetic changes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 5, May 2015, Pages 732-741
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 5, May 2015, Pages 732-741
نویسندگان
Sudhakar Veeranki, Lee J. Winchester, Suresh C. Tyagi,