Cardioprotective effect of adiponectin is partially mediated by its AMPK-independent antinitrative action
Cardioprotective effect of adiponectin is partially mediated by its AMPK-independent antinitrative action
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脂联素的心脏保护作用部分是由其不依赖于 AMPK 的抗硝作用介导的
DOI：
10.1152/ajpendo.90975.2008
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发表时间：
2009-08-01
影响因子：
5.1
通讯作者：
Ma, Xin-Liang
中科院分区：
文献类型：
--
作者：
Wang, Yajing;Tao, Ling;Ma, Xin-Liang
王毅，陶丽，袁毅，刘伟波，李瑞，洛佩斯BL，田瑞，马晓丽。脂联素的心肌保护作用部分由其AMPK非依赖性抗硝酸作用介导。Am J Physiol Endocrinol Metab 297：E384-E391，2009.首次发表于2009年5月26日; doi：10.1152ajpendo.90975.2008。脂联素（APN）主要通过腺苷酸依赖性蛋白激酶（AMPK）发挥其代谢调节作用。然而，AMPK在缺血再灌注（IR）成年心肌细胞中APN抗凋亡作用中的作用仍不完全清楚。本研究旨在确定AMPK参与APN的抗凋亡信号转导。将来自过表达AMPK的显性负性α 2-亚基（AMPK-DN）或野生型（WT）同窝出生的成年雄性小鼠的心肌细胞进行模拟IR（SIR），并用2 μ g/ml APN球状结构域（gAPN）或载体预处理。在AMPK-DN心肌细胞中，SIR诱导的心肌细胞凋亡适度增加（P < 0.05）。用gAPN处理显著减少WT心肌细胞以及AMPK-DN心肌细胞中SIR诱导的凋亡，表明gAPN的抗凋亡作用部分不依赖于AMPK。此外，在AMPK-DN心肌细胞中，gAPN诱导的内皮型一氧化氮合酶（eNOS）磷酸化显著降低，表明AMPK-DN心肌细胞中APN-eNOS信号传导轴受损。另外的实验表明，用gAPN处理AMPK-DN心肌细胞减少了SIR诱导的NADPH氧化酶过表达，减少了超氧化物的产生，并阻断了过氧亚硝酸盐的形成，其程度与在WT心肌细胞中观察到的相同。总的来说，我们目前的研究表明，虽然APN的代谢和eNOS激活作用在很大程度上是由AMPK介导的，但APN的超氧化物抑制作用不是由AMPK介导的，APN的这种AMPK独立的抗氧化特性增加了一氧化氮的生物利用度，并产生了显着的抗凋亡作用。
Wang Y, Tao L, Yuan Y, Lau WB, Li R, Lopez BL, Christopher TA, Tian R, Ma XL. Cardioprotective effect of adiponectin is partially mediated by its AMPK-independent antinitrative action. Am J Physiol Endocrinol Metab 297: E384-E391, 2009. First published May 26, 2009; doi: 10.1152ajpendo.90975.2008.-Adiponectin (APN) exerts its metabolic regulation largely through AMP-dependent protein kinase (AMPK). However, the role of AMPK in APN's antiapoptotic effect in ischemic-reperfused (IR) adult cardiomyocytes remains incompletely understood. The present study was designed to determine the involvement of AMPK in the antiapoptotic signaling of APN. Cardiomyocytes from adult male mice over-expressing a dominant-negative alpha 2-subunit of AMPK (AMPK-DN) or wildtype (WT) littermates were subjected to simulated IR (SIR) and pretreated with 2 mu g/ml globular domain of APN (gAPN) or vehicle. SIR-induced cardiomyocyte apoptosis was modestly increased in AMPK-DN cardiomyocytes (P < 0.05). Treatment with gAPN significantly reduced SIR-induced apoptosis in WT cardiomyocytes as well as in AMPK-DN cardiomyocytes, indicating that the antiapoptotic effect of gAPN is partially AMPK independent. Furthermore, gAPN-induced endothelial nitric oxide synthase (eNOS) phosphorylation was significantly reduced in AMPK-DN cardiomyocytes, suggesting that the APN-eNOS signaling axis is impaired in AMPK-DN cardiomyocytes. Additional experiments demonstrated that treatment of AMPK-DN cardiomyocytes with gAPN reduced SIR-induced NADPH oxidase overexpression, decreased superoxide generation, and blocked peroxynitrite formation to the same extent as that observed in WT cardiomyocytes. Collectively, our present study demonstrated that although the metabolic and eNOS activation effect of APN is largely mediated by AMPK, the superoxide-suppressing effect of APN is not mediated by AMPK, and this AMPK-independent antioxidant property of APN increased nitric oxide bioavailability and exerted significant antiapoptotic effect.