Activation of G protein-coupled oestrogen receptor 1 at the onset of reperfusion protects the myocardium against ischemia/reperfusion injury by reducing mitochondrial dysfunction and mitophagy.
Activation of G protein-coupled oestrogen receptor 1 at the onset of reperfusion protects the myocardium against ischemia/reperfusion injury by reducing mitochondrial dysfunction and mitophagy.
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DOI：
10.1111/bph.14033
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发表时间：
2017-12
影响因子：
7.3
通讯作者：
Bopassa JC
中科院分区：
文献类型：
--
作者：
Feng Y;Madungwe NB;da Cruz Junho CV;Bopassa JC
最近的证据表明，GPER（G 蛋白偶联雌激素受体 1）通过包括 PKC 易位、ERK1/2/GSK-3β 磷酸化和抑制线粒体通透性转换孔 (mPTP) 开放的信号级联反应，介导急性缺血前雌激素诱导的心肌免受缺血/再灌注损伤的保护。在这里，我们研究了缺血/再灌注损伤中缺血后 GPER 激活的影响和机制。我们确定再灌注开始时 GPER 激活是否通过防止线粒体损伤和线粒体自噬而产生心脏保护作用。 体内大鼠心脏遭受缺血，然后用雌激素（17β-雌二醇，E2）、E2 + G15、GPER 拮抗剂或载体进行再灌注。测量心肌梗死面积、mPTP 开放阈值、线粒体自噬、线粒体膜电位、ROS 产生、泛素化蛋白（包括亲环蛋白 D）以及 ERK 和 GSK-3β 的磷酸化水平。我们发现，对雄性和雌性卵巢切除大鼠进行缺血后给予 E2 可以减少心肌梗塞的面积。缺血后 E2 给药保留了线粒体结构完整性，这与 ROS 产生减少和线粒体膜电位增加以及通过激活 MEK/ERK/GSK-3β 轴诱导 mPTP 打开所需的线粒体 Ca2+ 负荷增加有关。此外，E2 通过涉及 LC3I、LC3II 和 p62 蛋白的 PINK1/Parkin 途径减少线粒体自噬。 E2 的所有这些缺血后效应均被 G15 消除，表明存在 GPER 依赖性机制。这些结果表明，缺血后 GPER 激活通过保护线粒体结构完整性和功能并减少线粒体自噬，对男性和女性的缺血/再灌注损伤产生心脏保护作用。
Recent evidence indicates that GPER (G protein‐coupled oestrogen receptor 1) mediates acute pre‐ischaemic oestrogen‐induced protection of the myocardium from ischaemia/reperfusion injury via a signalling cascade that includes PKC translocation, ERK1/2/ GSK‐3β phosphorylation and inhibition of the mitochondrial permeability transition pore (mPTP) opening. Here, we investigated the impact and mechanism involved in post‐ischaemic GPER activation in ischaemia/reperfusion injury. We determined whether GPER activation at the onset of reperfusion confers cardioprotective effects by protecting against mitochondrial impairment and mitophagy. In vivo rat hearts were subjected to ischaemia followed by reperfusion with oestrogen (17β‐oestradiol, E2), E2 + G15, a GPER antagonist, or vehicle. Myocardial infarct size, the threshold for the opening of mPTP, mitophagy, mitochondrial membrane potential, ROS production, proteins ubiquitinated including cyclophilin D, and phosphorylation levels of ERK and GSK‐3β were measured. We found that post‐ischaemic E2 administration to both male and female ovariectomized‐rats reduced myocardial infarct size. Post‐ischaemic E2 administration preserved mitochondrial structural integrity and this was associated with a decrease in ROS production and increased mitochondrial membrane potential, as well as an increase in the mitochondrial Ca2+ load required to induce mPTP opening via activation of the MEK/ERK/GSK‐3β axis. Moreover, E2 reduced mitophagy via the PINK1/Parkin pathway involving LC3I, LC3II and p62 proteins. All these post‐ischaemic effects of E2 were abolished by G15 suggesting a GPER‐dependent mechanism. These results indicate that post‐ischaemic GPER activation induces cardioprotective effects against ischaemia/reperfusion injury in males and females by protecting mitochondrial structural integrity and function and reducing mitophagy.
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影响因子：
3.5
作者：
ICHAS, F;JOUAVILLE, LS;HOLMUHAMEDOV, EL
通讯作者：
HOLMUHAMEDOV, EL
虎杖甙后处理可通过促进自噬通量减轻心肌缺血/再灌注损伤。
影响因子：
6
作者：
Ling, Yuanna;Chen, Guiming;Chen, Aihua
通讯作者：
Chen, Aihua
DOI：
10.1074/jbc.m109.025353
发表时间：
2009-07-31
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Baumgartner HK;Gerasimenko JV;Thorne C;Ferdek P;Pozzan T;Tepikin AV;Petersen OH;Sutton R;Watson AJ;Gerasimenko OV
通讯作者：
Gerasimenko OV
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
4
作者：
Floryk, D;Houstek, J
通讯作者：
Houstek, J