کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8270720 | 1534975 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ferritin heavy chain as main mediator of preventive effect of metformin against mitochondrial damage induced by doxorubicin in cardiomyocytes
ترجمه فارسی عنوان
زنجیره سنگین فریتین به عنوان میانجی کننده اصلی اثر پیشگیرانه متفورمین در برابر آسیب های میتوکندری ناشی از دوکسوروبیسین در قلب کوموموسیت ها
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کلمات کلیدی
RPAHBSSPMSFMPTPΔΨmCCCPDOXTNFαPBSNF-κBFHCIron Homeostasis - Homostasis آهنROS - ROSEDTA - اتیلن دی آمین تترا استیک اسید Ethylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدmitochondrial permeability transition pore - انتقال نفوذی میتوکندری منفی استterminal deoxynucleotidyl transferase dUTP nick-end labeling - ترمینال deoxynucleotidyl transferase dUTP نهایی پایان برچسبtumor necrosis factor-α - تومور نکروز عامل αTUNEL - تونلDoxorubicin - دوکسوروبیسینFree radicals - رادیکال آزادFerritin Heavy Chain - زنجیره سنگین فریتینCardiotoxicity - سمیت قلبیMitochondrial function - عملکرد میتوکندریnuclear factor κB - فاکتور هسته ای κBFerritin - فریتینphenylmethylsulfonyl fluoride - فنیل متیل سولفونیل فلورایدMetformin - متفورمینPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریHanks’ balanced salt solution - محلول نمک متعادل هانکسMET - ملاقات کردMitochondrial membrane potential - پتانسیل غشای میتوکندریcarbonyl cyanide m-chlorophenylhydrazone - کربنیل سیانید m-chlorophenylhydrazoneReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
چکیده انگلیسی
The efficacy of doxorubicin (DOX) as an antitumor agent is greatly limited by the induction of cardiomyopathy, which results from mitochondrial dysfunction and iron-catalyzed oxidative stress in the cardiomyocyte. Metformin (MET) has been seen to have a protective effect against the oxidative stress induced by DOX in cardiomyocytes through its modulation of ferritin heavy chain (FHC), the main iron-storage protein. This study aimed to assess the involvement of FHC as a pivotal molecule in the mitochondrial protection offered by MET against DOX cardiotoxicity. The addition of DOX to adult mouse cardiomyocytes (HL-1 cell line) increased the cytosolic and mitochondrial free iron pools in a time-dependent manner. Simultaneously, DOX inhibited complex I activity and ATP generation and induced the loss of mitochondrial membrane potential. The mitochondrial dysfunction induced by DOX was associated with the release of cytochrome c to the cytosol, the activation of caspase 3, and DNA fragmentation. The loss of iron homeostasis, mitochondrial dysfunction, and apoptosis induced by DOX were prevented by treatment with MET 24 h before the addition of DOX. The involvement of FHC and NF-κB was determined through siRNA-mediated knockdown. Interestingly, the presilencing of FHC or NF-κB with specific siRNAs blocked the protective effect induced by MET against DOX cardiotoxicity. These findings were confirmed in isolated primary neonatal rat cardiomyocytes. In conclusion, these results deepen our knowledge of the protective action of MET against DOX-induced cardiotoxicity and suggest that therapeutic strategies based on FHC modulation could protect cardiomyocytes from the mitochondrial damage induced by DOX by restoring iron homeostasis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 67, February 2014, Pages 19-29
Journal: Free Radical Biology and Medicine - Volume 67, February 2014, Pages 19-29
نویسندگان
Mari C. Asensio-Lopez, Jesus Sanchez-Mas, Domingo A. Pascual-Figal, Carlos de Torre, Mariano Valdes, Antonio Lax,