Adiponectin Facilitates Postconditioning Cardioprotection through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation
Adiponectin Facilitates Postconditioning Cardioprotection through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation
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脂联素通过 AMPK 依赖性核和 AMPK 独立线粒体 STAT3 激活促进后处理心脏保护
DOI：
10.1155/2020/4253457
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发表时间：
2020-03
影响因子：
--
通讯作者：
Xia Zhengyuan
中科院分区：
文献类型：
--
作者：
Zhu Qiqi;Li Haobo;Xie Xiang;Chen Xiaozhen;Kosuru Ramoji;Li Sisi;Lian Qingquan;Cheung Chi Wai;Irwin Michael G.;Ge Ren-shan;Xia Zhengyuan
心肌缺血后处理（IPo-）介导的抗心肌缺血再灌注（IR）损伤的作用需要信号转导子和转录激活子3（STAT 3）的激活，其中脂联素（APN）参与了这一过程。APN通过AMPK依赖性和非AMPK依赖性途径发挥其生物学作用。然而，AMPK在APN介导的STAT 3活化中在IPo心脏保护中的作用尚不清楚。我们假设APN介导的STAT 3激活在IPo中是AMPK非依赖性的，并且APN通过AMPK依赖性STAT 3激活促进IPo心脏保护。在这里，Sprague-Dawley大鼠进行心肌IR没有或有IPo和/或APN。APN或IPo可显著改善缺血后心功能，减轻心肌损伤和氧化应激，二者联合可进一步减轻缺血后心肌损伤。APN或其与IPo的组合而不是单独的IPo显著增加AMPK活化以及核和线粒体STAT 3活化，而IPo显著增强线粒体而不是核STAT 3活化。在主要分离的心肌细胞，重组球状APN（gAd），缺氧后处理（HPo），或其组合显着减弱缺氧/再氧诱导的细胞损伤和增加核和/或线粒体STAT 3激活。STAT 3抑制对gAd或gAd与HPo诱导的AMPK活化组合没有影响，但消除了它们的细胞保护作用。AMPK抑制不影响HPo心脏保护，但取消gAd心脏保护和禁用gAd促进/增强HPo心脏保护和STAT 3激活。这些结果表明，APN通过AMPK依赖性和AMPK非依赖性STAT 3激活赋予心脏保护，而IPo通过AMPK非依赖性线粒体STAT 3激活赋予心脏保护。APN和IPo联合使用通过不同的信号通路激活STAT 3协同减轻心肌IR损伤。
Myocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independent pathways. However, the role of AMPK in APN-mediated STAT3 activation in IPo cardioprotection is unknown. We hypothesized that APN-mediated STAT3 activation in IPo is AMPK-independent and that APN through AMPK-dependent STAT3 activation facilitates IPo cardioprotection. Here, Sprague-Dawley rats were subjected to myocardial IR without or with IPo and/or APN. APN or IPo significantly improved postischemic cardiac function and reduced myocardial injury and oxidative stress, and their combination further attenuated postischemic myocardial injuries. APN or its combination with IPo but not IPo alone significantly increased AMPK activation and both nuclear and mitochondrial STAT3 activation, while IPo significantly enhanced mitochondrial but not nuclear STAT3 activation. In primarily isolated cardiomyocytes, recombined globular APN (gAd), hypoxic postconditioning (HPo), or their combination significantly attenuated hypoxia/reoxygenation-induced cell injury and increased nuclear and/or mitochondrial STAT3 activation. STAT3 inhibition had no impact on gAd or gAd in combination with HPo-induced AMPK activation but abolished their cellular protective effects. AMPK inhibition did not affect HPo cardioprotection but abolished gAd cardioprotection and disabled gAd to facilitate/enhance HPo cardioprotection and STAT3 activation. These results suggest that APN confers cardioprotection through AMPK-dependent and AMPK-independent STAT3 activation, while IPo confers cardioprotection through AMPK-independent mitochondrial STAT3 activation. Joint use of APN and IPo synergistically attenuated myocardial IR injury by activating STAT3 via distinct signaling pathways.
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DOI：
10.1126/science.1164551
发表时间：
2009-02-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Wegrzyn J;Potla R;Chwae YJ;Sepuri NB;Zhang Q;Koeck T;Derecka M;Szczepanek K;Szelag M;Gornicka A;Moh A;Moghaddas S;Chen Q;Bobbili S;Cichy J;Dulak J;Baker DP;Wolfman A;Stuehr D;Hassan MO;Fu XY;Avadhani N;Drake JI;Fawcett P;Lesnefsky EJ;Larner AC
通讯作者：
Larner AC
影响因子：
3.7
作者：
Wang T;Qiao S;Lei S;Liu Y;Ng KF;Xu A;Lam KS;Irwin MG;Xia Z
通讯作者：
Xia Z
AdipoRon 是第一个口服活性脂联素受体激活剂，通过 AMPK 介导和 AMPK 独立信号传导减弱缺血后心肌细胞凋亡。
DOI：
10.1152/ajpendo.00577.2014
发表时间：
2015-08-01
影响因子：
5.1
作者：
Zhang, Yanqing;Zhao, Jianli;Wang, Ya-Jing
通讯作者：
Wang, Ya-Jing
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
发表时间：
2009-08-01
影响因子：
5.1
作者：
Wang, Yajing;Tao, Ling;Ma, Xin-Liang
通讯作者：
Ma, Xin-Liang
影响因子：
10.8
作者：
Kin, H;Zhao, ZQ;Vinten-Johansen, J
通讯作者：
Vinten-Johansen, J