Department of Biomedical Sciences and Human Oncology-Pharmacology Section, Medical School-University of Bari "Aldo Moro", Bari, Italy.
Department of Emergency and Organ Transplantation-Section of Cardiovascular Diseases, Medical School-University of Bari "Aldo Moro", Bari, Italy.
PLoS One. 2019 Jan 17;14(1):e0210654. doi: 10.1371/journal.pone.0210654. eCollection 2019.
Adiponectin (AD) cardioprotective activities are mediated by AMPK, a fuel-sensing molecule sharing common targets and cellular activities with SIRT-1. Whether AD preconditioning may involve SIRT-1 activity is not known; however, the protective role of SIRT-1 during ischemia and the potential interplay between AMPK and SIRT-1 suggest this possibility.
Isolated hearts from male Sprague-Dawley rats (n = 85) underwent ischemia/reperfusion (I/R, 30/180 min). Preconditioning with resveratrol (RSV, SIRT-1 activator) was compared to preconditioning with AD alone, or in combination with compound C (CC, AMPK inhibitor) or sirtinol (STN, SIRT-1 inhibitor). For each heart, left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (dLVP), coronary flow (CF) and left ventricular infarct mass (IM) were measured, together with the phosphorylation/activation status of AMPK, LKB1, eNOS and SIRT-1, at the beginning (15 min) and at the end (180 min) of reperfusion.
When compared to I/R, both RSV and AD improved cardiac function and reduced IM (p < 0.01, p < 0.05, respectively). Cardioprotective effects of AD were completely reversed in the AD+CC group, and significantly attenuated in the AD+STN group. Both RSV and AD increased eNOS, AMPK and LKB1 phosphorylation (for each parameter: p < 0.05 vs. I/R, in both RSV and AD treatment groups) at 15 min of reperfusion, and SIRT-1 activity at the end of reperfusion (p < 0.01, p < 0.05 vs. I/R, respectively). Interestingly, AD-mediated phosphorylation of AMPK and LKB1, and SIRT-1 deacetylation activity was markedly reduced in both the AD+CC and AD+STN groups (p < 0.05 vs. AD). Thus, AD-mediated cardioprotection requires both AMPK and SIRT-1 signaling pathways, that act as a component of a cycle and regulate each other's activities.
脂联素 (AD) 的心脏保护作用是通过 AMPK 介导的，AMPK 是一种与 SIRT-1 共享共同靶点和细胞活动的燃料感应分子。AD 预处理是否可能涉及 SIRT-1 活性尚不清楚；然而，SIRT-1 在缺血期间的保护作用以及 AMPK 和 SIRT-1 之间的潜在相互作用表明了这种可能性。
雄性 Sprague-Dawley 大鼠（n = 85）的离体心脏经历缺血/再灌注（I/R，30/180 分钟）。与单独使用 AD 预处理相比，用白藜芦醇（RSV，SIRT-1 激活剂）或 AD 与化合物 C（CC，AMPK 抑制剂）或 Sirtinol（STN，SIRT-1 抑制剂）联合预处理。对于每个心脏，测量左心室舒张末期压（LVEDP）、左心室发展压（dLVP）、冠状动脉流量（CF）和左心室梗死质量（IM），以及再灌注开始时（15 分钟）和结束时（180 分钟）的 AMPK、LKB1、eNOS 和 SIRT-1 的磷酸化/激活状态。
与 I/R 相比，RSV 和 AD 均改善了心功能并减少了 IM（p < 0.01，p < 0.05）。AD+CC 组 AD 的心脏保护作用完全逆转，AD+STN 组明显减弱。RSV 和 AD 均增加了 eNOS、AMPK 和 LKB1 的磷酸化（对于每个参数：与 I/R 相比，在 RSV 和 AD 治疗组中均为 p < 0.05），以及再灌注结束时的 SIRT-1 活性（p < 0.01，p < 0.05，分别与 I/R 相比）。有趣的是，AD 介导的 AMPK 和 LKB1 的磷酸化以及 SIRT-1 的去乙酰化活性在 AD+CC 和 AD+STN 组中均明显降低（与 AD 相比，p < 0.05）。因此，AD 介导的心脏保护作用需要 AMPK 和 SIRT-1 信号通路，它们作为一个循环的组成部分并调节彼此的活性。
