Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.
Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.
复制标题
DOI：
10.1002/jcp.25413
复制
发表时间：
2017-01
影响因子：
5.6
通讯作者：
Bosnjak, Zeljko J.
中科院分区：
文献类型：
--
作者：
Sedlic, Filip;Muravyeva, Maria Y.;Sepac, Ana;Sedlic, Marija;Williams, Anna Marie;Yang, Meiying;Bai, Xiaowen;Bosnjak, Zeljko J.
关于糖尿病和高血糖对心肌梗塞影响的相互矛盾的报道从细胞毒性到细胞保护。该研究旨在研究高葡萄糖驱动的线粒体代谢和渗透压变化对离体大鼠心肌细胞的适应性机制和氧化应激抵抗力的急性影响。我们研究了高葡萄糖对线粒体生物能学几个参数的影响，包括耗氧量、线粒体膜电位和 NAD(P)H 荧光测定的变化。还测试了高葡萄糖对麻醉预处理（APC）引起的内源性细胞保护机制和细胞损伤介质的影响。这些实验包括通过激光扫描荧光共聚焦显微镜实时测量单细胞中活性氧（ROS）的产生和线粒体通透性转换孔（mPTP）的开放，以及细胞存活测定。通过 NAD(P)H 荧光强度、耗氧量和线粒体膜电位的增加观察到高葡萄糖迅速增强线粒体能量代谢。这大大增加了 ROS 的产生，加速了 mPTP 的开放，并降低了暴露于氧化应激的细胞的存活率。用 2,4 二硝基苯酚 (DNP) 消除高葡萄糖诱导的线粒体超极化可显着但不完全地将 ROS 产生减弱至与高渗甘露醇对照相似的水平。 DNP 治疗将高葡萄糖诱导的细胞毒性逆转为细胞保护。高渗甘露醇治疗也诱导细胞保护。高葡萄糖消除了 APC 诱导的线粒体去极化、mPTP 开放延迟和细胞保护。总之，高葡萄糖诱导的线粒体超极化会消除 APC 并加剧细胞损伤。通过消除线粒体超极化来减弱高葡萄糖诱导的 ROS 产生，从而保护心肌细胞。
Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential and NAD(P)H fluorometry. Effects of high glucose on the endogenous cytoprotective mechanisms elicited by anesthetic preconditioning (APC) and the mediators of cell injury were also tested. These experiments included real-time measurements of reactive oxygen species (ROS) production and mitochondrial permeability transition pore (mPTP) opening in single cells by laser scanning fluorescence confocal microscopy, and cell survival assay. High glucose rapidly enhanced mitochondrial energy metabolism, observed by increase in NAD(P)H fluorescence intensity, oxygen consumption and mitochondrial membrane potential. This substantially elevated production of ROS, accelerated opening of the mPTP and decreased survival of cells exposed to oxidative stress. Abrogation of high glucose-induced mitochondrial hyperpolarization with 2,4 dinitrophenol (DNP) significantly, but not completely, attenuated ROS production to a level similar to hyperosmotic mannitol control. DNP treatment reversed high glucose-induced cytotoxicity to cytoprotection. Hyperosmotic mannitol treatment also induced cytoprotection. High glucose abrogated APC-induced mitochondrial depolarization, delay in mPTP opening and cytoprotection. In conclusion, high glucose-induced mitochondrial hyperpolarization abolishes APC and augments cell injury. Attenuation of high glucose-induced ROS production by eliminating mitochondrial hyperpolarization protects cardiomyocytes.
登录
查看更多内容
影响因子：
2.9
作者：
ESTABROOK, RW
通讯作者：
ESTABROOK, RW
影响因子：
37.8
作者：
LIU, YG;THORNTON, JD;SCHAFFER, SW
通讯作者：
SCHAFFER, SW
影响因子：
8.8
作者：
Canfield SG;Sepac A;Sedlic F;Muravyeva MY;Bai X;Bosnjak ZJ
通讯作者：
Bosnjak ZJ
DOI：
10.1152/ajpheart.00711.2002
发表时间：
2003-02-01
影响因子：
4.8
作者：
Kevin, LG;Camara, AKS;Stowe, DF
通讯作者：
Stowe, DF
DOI：
10.1152/ajpheart.00850.2012
发表时间：
2013-07-01
影响因子：
4.8
作者：
Baotic, Ines;Ge, Zhi-Dong;Kersten, Judy R.
通讯作者：
Kersten, Judy R.