Exogenous H2S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes.
Exogenous H2S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes.
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外源性 H2S 调节内质网-线粒体串扰抑制 STZ 诱导的 I 型糖尿病的细胞凋亡途径
DOI：
10.1152/ajpendo.00196.2016
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Yang F;Yu X;Li T;Wu J;Zhao Y;Liu J;Sun A;Dong S;Wu J;Zhong X;Xu C;Lu F;Zhang W
活性氧（ROS）的上调是糖尿病心肌病（DCM）心肌细胞凋亡的主要原因。线粒体融合蛋白-2（Mfn-2）是连接线粒体和内质网（ER）的关键蛋白。硫化氢（H2S）介导的心脏保护作用与抗氧化作用有关。本研究表明，H2S抑制ER和线粒体凋亡途径之间的相互作用。本研究探讨了STZ诱导的I型糖尿病大鼠心脏功能，ER和线粒体的超微结构变化，凋亡率，TUNEL法，ER应激相关蛋白和线粒体凋亡蛋白的表达在心脏组织中的STZ诱导的I型糖尿病大鼠治疗或不治疗NaHS（供体H2S）。分离心肌线粒体，检测MPTP开放、细胞色素C（cyt C）和Mfn-2表达。我们的数据表明，高血糖降低心脏功能的超声心动图，和外源性H2S的管理改善这些变化。我们证明，ER应激传感器的表达和细胞凋亡率在DCM的心脏组织和培养的H9 C2细胞中升高，但这些蛋白质的表达降低后外源性H2S处理。线粒体凋亡蛋白，细胞色素C，和mPTP开放的表达与外源性H2S处理后下降。在本实验中，转染Mfn-2-siRNA后，Mfn-2的表达和免疫荧光均降低。高血压刺激ER的相互作用和线粒体凋亡途径，这是抑制外源性H2S处理通过调节Mfn-2的表达。
The upregulation of reactive oxygen species (ROS) is a primary cause of cardiomyocyte apoptosis in diabetes cardiomyopathy (DCM). Mitofusin-2 (Mfn-2) is a key protein that bridges the mitochondria and endoplasmic reticulum (ER). Hydrogen sulfide (H2S)-mediated cardioprotection is related to antioxidant effects. The present study demonstrated that H2S inhibited the interaction between the ER and mitochondrial apoptotic pathway. This study investigated cardiac function, ultrastructural changes in the ER and mitochondria, apoptotic rate using TUNEL, and the expression of ER stress-associated proteins and mitochondrial apoptotic proteins in cardiac tissues in STZ-induced type I diabetic rats treated with or without NaHS (donor of H2S). Mitochondria of cardiac tissues were isolated, and MPTP opening and cytochrome c (cyt C) and Mfn-2 expression were also detected. Our data showed that hyperglycemia decreased the cardiac function by ultrasound cardiogram, and the administration of exogenous H2S ameliorated these changes. We demonstrated that the expression of ER stress sensors and apoptotic rates were elevated in cardiac tissue of DCM and cultured H9C2 cells, but the expression of these proteins was reduced following exogenous H2S treatment. The expression of mitochondrial apoptotic proteins, cyt C, and mPTP opening was decreased following treatment with exogenous H2S. In our experiment, the expression and immunofluorescence of Mfn-2 were both decreased after transfection with Mfn-2-siRNA. Hyperglycemia stimulated ER interactions and mitochondrial apoptotic pathways, which were inhibited by exogenous H2S treatment through the regulation of Mfn-2 expression.
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影响因子：
3
作者：
Cicek, Figen Amber;Toy, Aysegul;Turan, Belma
通讯作者：
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影响因子：
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作者：
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DOI：
--
发表时间：
2018
期刊：
--
影响因子：
--
作者：
Michael Smith;David Brink
通讯作者：
Michael Smith;David Brink
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