کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2129917 1086511 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
FGF21 represses cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 signaling pathway in an AMPK-dependent manner
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
FGF21 represses cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 signaling pathway in an AMPK-dependent manner
چکیده انگلیسی


• FGF21 restricts Ang II-induced senescence in hBVSMCs.
• FGF21 suppresses Ang II-induced oxidant stress in hBVSMCs.
• FGF21 inhibits Ang II-mediated mitochondrial dysfunction in hBVSMCs.
• FGF21 reduces Ang II-mediated p53 activation in hBVSMCs.
• Activation of AMPK contributes to the anti-aging action of FGF21 in hBVSMCs.

Cerebrovascular aging has a high relationship with stroke and neurodegenerative disease. In the present study, we evaluated the influence of fibroblast growth factor 21 (FGF21) on angiotensin (Ang II)-mediated cerebrovascular aging in human brain vascular smooth muscle cells (hBVSMCs). Ang II induced remarkable aging-phenotypes in hBVSMCs, including enhanced SA-β-gal staining and NBS1 protein expression. First, we used immunoblotting assay to confirm protein expression of FGF21 receptor (FGFR1) and the co-receptor β-Klotho in cultured hBVSMCs. Second, we found that FGF21 treatment partly prevented the aging-related changes induced by Ang II. FGF21 inhibited Ang II-enhanced ROS production/superoxide anion levels, rescued the Ang II-reduced Complex IV and citrate synthase activities, and suppressed the Ang II-induced meprin protein expression. Third, we showed that FGF21 not only inhibited the Ang II-induced p53 activation, but also blocked the action of Ang II on Siah-1-TRF signaling pathway which is upstream factors for p53 activation. At last, either chemical inhibition of AMPK signaling pathway by a specific antagonist Compound C or knockdown of AMPKα1/2 isoform using siRNA, successfully abolished the anti-aging action of FGF21 in hBVSMCs. These results indicate that FGF21 protects against Ang II-induced cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 activation in an AMPK-dependent manner, and highlight the therapeutic value of FGF21 in cerebrovascular aging-related diseases such as stroke and neurodegenerative disease.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 346, Issue 2, 15 August 2016, Pages 147–156
نویسندگان
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