Extracellular Cl--free-induced cardioprotection against hypoxia/reoxygenation is associated with attenuation of mitochondrial permeability transition pore.
Extracellular Cl--free-induced cardioprotection against hypoxia/reoxygenation is associated with attenuation of mitochondrial permeability transition pore.
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细胞外无氯诱导的针对缺氧/复氧的心脏保护作用与线粒体通透性转换孔的减弱有关。
DOI：
10.1016/j.biopha.2016.12.048
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Chen He-Ping
中科院分区：
文献类型：
--
作者：
Zhang Xian-Gui;Zhao Le;Zhang Yi;Li Yuan-Yuan;Wang Huan;Duan Guang-Ling;Xiao Lin;Li Xiao-Ran;Chen He-Ping
葡萄糖酸盐等渗取代细胞外氯离子（细胞外无Cl−）已被证明可以通过降低缺血/再灌注引起的细胞内氯离子浓度升高（[Cl−]i）而引起心脏保护。然而，细胞外无Cl−的心脏保护作用的下游机制尚未完全确定。本研究探讨了细胞外无Cl -是否能减弱缺氧/再氧化（H/R）后的线粒体功能障碍，以及线粒体通透性过渡孔（mPTP）是否在细胞外无Cl -心脏保护中起关键作用。在H/R期间，H9c2细胞用或不含Cl−的溶液孵育，其中Cl−被等量葡萄糖酸盐取代。mPTP的参与是用白术苷（Atr）确定的，白术苷是一种特殊的mPTP开启剂。结果表明，胞外无Cl−的减毒H/ r诱导[Cl−]i升高，细胞活力增加，乳酸脱氢酶释放减少。此外，胞外无Cl−抑制mPTP开放，改善线粒体功能，线粒体膜电位和呼吸链复合物活性得以保存，线粒体活性氧生成减少，ATP含量增加。有趣的是，Atr药理学打开mPTP减弱了细胞外无Cl−引起的所有保护作用，包括mPTP打开的抑制、线粒体膜电位的维持以及随后线粒体功能的改善。这些结果表明，细胞外Cl -free可保护H9c2细胞线粒体免受H/R损伤，抑制mPTP开放是介导细胞外Cl -free对心脏保护的关键步骤。
The isotonic substitution of extracellular chloride by gluconate (extracellular Cl−-free) has been demonstrated to elicit cardioprotection by attenuating ischaemia/reperfusion-induced elevation of intracellular chloride ion concentration ([Cl−]i). However, the downstream mechanism underlying the cardioprotective effect of extracellular Cl−-free is not fully established. Here, it was investigated whether extracellular Cl−-free attenuates mitochondrial dysfunction after hypoxia/reoxygenation (H/R) and whether mitochondrial permeability transition pore (mPTP) plays a key role in the extracellular Cl−-free cardioprotection. H9c2 cells were incubated with or without Cl−-free solution, in which Cl−was replaced with equimolar gluconate, during H/R. The involvement of mPTP was determined with atractyloside (Atr), a specific mPTP opener. The results showed that extracellular Cl−-free attenuated H/R-induced the elevation of [Cl−]i, accompanied by increase of cell viability and reduction of lactate dehydrogenase release. Moreover, extracellular Cl−-free inhibited mPTP opening, and improved mitochondria function, as indicated by preserved mitochondrial membrane potential and respiratory chain complex activities, decreased mitochondrial reactive oxygen species generation, and increased ATP content. Intriguingly, pharmacologically opening of the mPTP with Atr attenuated all the protective effects caused by extracellular Cl−-free, including suppression of mPTP opening, maintenance of mitochondrial membrane potential, and subsequent improvement of mitochondrial function. These results indicated that extracellular Cl−-free protects mitochondria from H/R injury in H9c2 cells and inhibition of mPTP opening is a crucial step in mediating the cardioprotection of extracellular Cl−-free.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
影响因子：
--
作者：
Jie Chen;Dan Liu;He-Ping Chen;Z. Liao;Z. Lai;M. He
通讯作者：
Jie Chen;Dan Liu;He-Ping Chen;Z. Liao;Z. Lai;M. He
影响因子：
3.1
作者：
Cheuk-Kwan Sun;Xing-yi Zhang;P. Sheard;A. Mabuchi;A. Wheatley
通讯作者：
Cheuk-Kwan Sun;Xing-yi Zhang;P. Sheard;A. Mabuchi;A. Wheatley
DOI：
--
发表时间：
2002-04
期刊：
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
影响因子：
--
作者：
Z. Lai
通讯作者：
Z. Lai
DOI：
10.1016/s0021-9258(19)50355-6
发表时间：
1992-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Bernardi
通讯作者：
P. Bernardi