کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8450250 | 1547681 | 2018 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Aldolase promotes the development of cardiac hypertrophy by targeting AMPK signaling
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Metabolic dysfunction is a hallmark of cardiac hypertrophy and heart failure. During cardiac failure, the metabolism of cardiomyocyte switches from fatty acid oxidation to glycolysis. However, the roles of key metabolic enzymes in cardiac hypertrophy are not understood fully. Here in the present work, we identified Aldolase A (AldoA) as a core regulator of cardiac hypertrophy. The mRNA and protein levels of AldoA were significantly up-regulated in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced hypertrophic mouse hearts. Overexpression of AldoA in cardiomyocytes promoted ISO-induced cardiomyocyte hypertrophy, whereas AldoA knockdown repressed cardiomyocyte hypertrophy. In addition, adeno-associated virus 9 (AAV9)-mediated in vivo knockdown of AldoA in the hearts rescued ISO-induced decrease in cardiac ejection fraction and fractional shortening and repressed cardiac hypertrophy. Mechanism study revealed that AldoA repressed the activation of AMP-dependent protein kinase (AMPK) signaling in a liver kinase B1 (LKB1)-dependent and AMP-independent manner. Inactivation of AMPK is a core mechanism underlying AldoA-mediated promotion of ISO-induced cardiomyocyte hypertrophy. By contrast, activation of AMPK with metformin and AICAR blocked AldoA function during cardiomyocyte hypertrophy. In summary, our data support the notion that AldoA-AMPK axis is a core regulatory signaling sensing energetic status and participates in cardiac hypertrophy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 370, Issue 1, 1 September 2018, Pages 78-86
Journal: Experimental Cell Research - Volume 370, Issue 1, 1 September 2018, Pages 78-86
نویسندگان
Yapeng Li, Dianhong Zhang, Lingyao Kong, Huiting Shi, Xinyu Tian, Lu Gao, Yuzhou Liu, Leiming Wu, Binbin Du, Zhen Huang, Cui Liang, Zheng Wang, Rui Yao, Yanzhou Zhang,