Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt.
Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt.
复制标题
内源性硫化氢途径的下调参与高盐诱导的线粒体相关内皮细胞凋亡
DOI：
10.1155/2015/754670
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发表时间：
2015
影响因子：
--
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Zong Y;Huang Y;Chen S;Zhu M;Chen Q;Feng S;Sun Y;Zhang Q;Tang C;Du J;Jin H
背景本研究旨在探讨内源性H2S通路是否参与了高盐诱导的血管内皮细胞凋亡。方法.培养的人脐静脉内皮细胞（HUVEC）用于研究。检测上清液中H2S含量。Western blot检测胱硫醚γ-裂解酶（CSE）、切割型半胱天冬酶-3（cleaved-caspase-3）、线粒体和胞浆细胞色素c（cytc）的表达。用荧光探针定量检测HUVEC超氧阴离子的产生和原位测定超氧阴离子的产生。线粒体膜孔开放，线粒体膜电位和caspase-9活性进行了测量。采用细胞死亡ELISA法和末端转移酶介导的dUTP缺口末端标记法（TUNEL）检测细胞凋亡。结果高盐处理下调了内源性VEC H2S/CSE通路，增加了氧自由基的产生，降低了线粒体膜电位，增加了线粒体膜通透性转换孔的开放和线粒体细胞色素c的渗漏，激活了细胞质caspase-9和caspase-3，诱导VEC凋亡。然而，补充H2S供体可显著抑制高盐诱导的VEC氧化应激和血管内皮细胞凋亡。结论H2S/CSE通路是内皮细胞对抗高盐损伤的重要内源性防御系统。其保护机制可能与抑制氧化应激和保护线粒体损伤有关。
Background. The study aimed to investigate whether endogenous H2S pathway was involved in high-salt-stimulated mitochondria-related vascular endothelial cell (VEC) apoptosis. Methods. Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. H2S content in the supernatant was detected. Western blot was used to detect expression of cystathionine gamma-lyase (CSE), cleaved-caspase-3, and mitochondrial and cytosolic cytochrome c (cytc). Fluorescent probes were used to quantitatively detect superoxide anion generation and measure the in situ superoxide anion generation in HUVEC. Mitochondrial membrane pore opening, mitochondrial membrane potential, and caspase-9 activities were measured. The cell apoptosis was detected by cell death ELISA and TdT-mediated dUTP nick end labeling (TUNEL) methods. Results. High-salt treatment downregulated the endogenous VEC H2S/CSE pathway, in association with increased generation of oxygen free radicals, decreased mitochondrial membrane potential, enhanced the opening of mitochondrial membrane permeability transition pore and leakage of mitochondrial cytc, activated cytoplasmic caspase-9 and caspase-3 and subsequently induced VEC apoptosis. However, supplementation of H2S donor markedly inhibited VEC oxidative stress and mitochondria-related VEC apoptosis induced by high salt. Conclusion. H2S/CSE pathway is an important endogenous defensive system in endothelial cells antagonizing high-salt insult. The protective mechanisms for VEC damage might involve inhibiting oxidative stress and protecting mitochondrial injury.
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DOI：
10.1126/science.1162667
发表时间：
2008-10-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yang G;Wu L;Jiang B;Yang W;Qi J;Cao K;Meng Q;Mustafa AK;Mu W;Zhang S;Snyder SH;Wang R
通讯作者：
Wang R
影响因子：
5
作者：
Pan, TT;Feng, ZN;Bian, JS
通讯作者：
Bian, JS
影响因子：
0.7
作者：
Mudau M;Genis A;Lochner A;Strijdom H
通讯作者：
Strijdom H
影响因子：
2.2
作者：
Jeffery, Jinny;Ayling, Ruth M.;McGonigle, Richard J. S.
通讯作者：
McGonigle, Richard J. S.
影响因子：
8.3
作者：
Schmidlin, Olga;Forman, Alex;Morris, R. Curtis, Jr.
通讯作者：
Morris, R. Curtis, Jr.