کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474871 | 1550433 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nrf2 enhances myocardial clearance of toxic ubiquitinated proteins
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
ANFαMHCBAFA1βMHCNQO1nuclear factor erythroid-2 related factor 2BNPLC3TACNrf2NAD(P)H:quinone oxidoreductase - NAD (P) H: کینون اکسیدوردوکتازROS - ROSAngiotensin II - آنژیوتانسین دوAutophagy - اتوفاژیCardiac dysfunction - اختلال قلبیbafilomycin A1 - بافیلومایسین A1Oxidative stress - تنش اکسیداتیوThioredoxin-1 - تیورودوکسین-1Ang II - دومbeta-myosin heavy chain - زنجیره سنگین بتا-میوزینUbiquitin proteasome system - سیستم پروتئازوم Ubiquitinatrial natriuretic factor - فاکتور natriuretic دهلیزیSERCA - قلبNecrosis - نکروز یا بافتمردگیmicrotubule-associated protein 1 light chain 3 - پروتئین مرتبط با میکروتوبول 1 زنجیره سبک 3Proteinopathy - پروتئینوپاتیReactive oxygen species - گونههای فعال اکسیژنUPS - یو پی اس
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a master transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes. While knockout of Nrf2 exaggerates cardiac pathological remodeling and dysfunction in diverse pathological settings, pharmacological activation of Nrf2 protects against cardiomyocyte injury and cardiac dysfunction. In contrast, there is also a concern that the chronic activation of Nrf2 secondary to oxidative stress is a contributing mechanism for the reductive stress-mediated heart failure. However, a direct link between cardiac specific activation of Nrf2 and cardiac protection or dysfunction in vivo remains to be established. Therefore, we investigated the effect of cardiomyocyte-specific transgenic activation of Nrf2 (Nrf2ctg) on cardiac pathological remodeling and dysfunction. We found that the cardiomyocyte-specific activation of Nrf2 suppressed myocardial oxidative stress as well as cardiac apoptosis, fibrosis, hypertrophy, and dysfunction in a setting of sustained pressure overload induced by transverse aortic arch constriction (TAC) in mice. Notably, the constitutive activation of Nrf2 increased the steady level of autophagosomes while decreasing the ubiquitinated protein aggregates in the heart after TAC. Nrf2 gene gain- and loss-of-function approaches revealed that Nrf2 enhances autophagosome formation and autophagic flux in cardiomyocytes. Unexpectedly, while Nrf2 minimally regulated apoptosis, it suppressed significantly the proteotoxic necrosis in cardiomyocytes. In addition, Nrf2 attenuated the proteocytotoxicity presumably via enhancing autophagy-mediated clearance of ubiquitinated protein aggregates in cardiomyocytes. Taken together, we demonstrated for the first time that cardiac specific activation of Nrf2 suppresses cardiac maladaptive remodeling and dysfunction most likely by enhancing autophagic clearance of toxic protein aggregates in the heart.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 72, July 2014, Pages 305-315
Journal: Journal of Molecular and Cellular Cardiology - Volume 72, July 2014, Pages 305-315
نویسندگان
Wenjuan Wang, Siying Li, Hui Wang, Bin Li, Lei Shao, Yimu Lai, Gary Horvath, Qian Wang, Masayuki Yamamoto, Joseph S. Janicki, Xing Li Wang, Dongqi Tang, Taixing Cui,