PICOT alleviates myocardial ischemia-reperfusion injury by reducing intracellular levels of reactive oxygen species
PICOT alleviates myocardial ischemia-reperfusion injury by reducing intracellular levels of reactive oxygen species
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DOI：
10.1016/j.bbrc.2017.02.136
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发表时间：
2017-04-15
影响因子：
3.1
通讯作者：
Park, Woo Jin
中科院分区：
文献类型：
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作者：
Kim, Jihwa;Kim, Jooyeon;Park, Woo Jin
活性氧（reactive oxygen species，ROS）的过量产生是心肌缺血再灌注（ischemia-reperfusion，I/R）损伤的主要原因之一。在这项研究中，我们研究了蛋白激酶C相互作用的硫氧还蛋白（PICOT; Grx 3）的表亲在心肌I/R使用PICOT转基因（TG）和敲低（KD）小鼠。PICOT TG小鼠的梗死和凋亡减弱，但PICOT KD小鼠在I/R时加重。同时，I/R诱导的ROS产生在PICOT TG小鼠中减弱，但在PICOT KID小鼠中加剧。血管紧张素II（AngI）介导的ROS和游离铁水平的增加也在PICOT TG小鼠分离的心肌细胞中减弱，但在PICOT KD小鼠的心肌细胞中加剧。因此，H2 O2介导的细胞死亡在PICOT TG小鼠分离的心肌细胞中减弱，但在PICOT KD小鼠的心肌细胞中加剧。总之，这些数据表明PICOT通过调节细胞内ROS和游离铁水平来减轻心肌I/R损伤。我们认为PICOT为心肌I/R损伤提供了一种新的治疗策略。(C)2017爱思唯尔公司All rights reserved.
Excessive generation of reactive oxygen species (ROS) is one of the main causes of myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the role of protein kinase C-interacting cousin of thioredoxin (PICOT; Grx3) during myocardial I/R using PICOT transgenic (TG) and knockdown (KD) mice. Infarction and apoptosis were attenuated in PICOT TG mice but exacerbated in PICOT KD mice upon I/R. In parallel, I/R-induced generation of ROS was attenuated in PICOT TG mice but exacerbated in PICOT KID mice. Angiotensin II (AnglI)-mediated increases in ROS and free iron levels were also attenuated in cardiomyocytes isolated from PICOT TG mice but exacerbated in cardiomyocytes from PICOT KD mice. Accordingly, H2O2-mediated cell death was attenuated in cardiomyocytes isolated from PICOT TG mice but exacerbated in cardiomyocytes from PICOT KD mice. Taken together, these data show that PICOT alleviates myocardial I/R injury by regulating intracellular ROS and free iron levels. We suggest that PICOT presents a novel therapeutic strategy for myocardial I/R injury. (C) 2017 Elsevier Inc. All rights reserved.