Hydrogen Sulfide Attenuates Hyperhomocysteinemia-Induced Cardiomyocytic Endoplasmic Reticulum Stress in Rats
Hydrogen Sulfide Attenuates Hyperhomocysteinemia-Induced Cardiomyocytic Endoplasmic Reticulum Stress in Rats
复制标题
硫化氢减轻大鼠高同型半胱氨酸血症引起的心肌细胞内质网应激
DOI：
10.1089/ars.2009.2898
复制
发表时间：
2010-05-01
影响因子：
6.6
通讯作者：
Du, Junbao
中科院分区：
文献类型：
--
作者：
Wei, Hongling;Zhang, Rongyuan;Du, Junbao
硫化氢（H2S）的心脏保护作用的机制尚不清楚。本研究旨在探讨H2S对高同型半胱氨酸血症（HHcy）诱导的心肌细胞内质网（ER）应激的调节作用。制备HHcy大鼠模型，培养H9 c2细胞（大鼠胚胎心脏来源的细胞系）。采用高效液相色谱法测定血浆同型半胱氨酸水平。用硫敏感电极测定血浆H2S浓度和心肌H2S产生。共聚焦免疫荧光分析心肌细胞C/EBP同源蛋白（CHOP）。Western blotting法检测心肌组织中葡萄糖调节蛋白78（GRP 78）、CHOP、caspase 12的表达及H9 c2细胞中切割型caspase 12和p-eIF 2 α的表达。结果表明，蛋氨酸超载诱导HHcy，导致显着的心肌细胞内质网应激，而内源性H2S的产生减少在HHcy大鼠。然而，H2S补充降低ER应激相关蛋白的表达，包括GRP 78，CHOP和caspase 12，由心肌组织在体内。抑制内源性H2S产生进一步增强心肌细胞ER应激，但H2S补充剂有效地拮抗了H9 c2细胞CHOP，裂解caspase 12和p-eIF 2a表达诱导的Hcy，毒胡萝卜素，或衣霉素在体外。结果表明，H2S可以减轻HHcy诱导的心肌细胞损伤中的心肌细胞内质网应激。抗氧化剂。氧化还原信号。12，1079-1091。
The mechanisms responsible for the cardioprotective effect of hydrogen sulfide (H2S) are unclear. The present study was designed to examine whether H2S could regulate hyperhomocysteinemia (HHcy)-induced cardiomyocytic endoplasmic reticulum (ER) stress. A rat model of HHcy was produced, and H9c2 cells (rat embryonic heart-derived cell line) were cultured. The plasma homocysteine was measured by using HPLC. Plasma H2S concentration and myocardial H2S production were measured with a sulfide-sensitive electrode. Confocal immunofluorescent analysis for cardiomyocytic C/EBP homologous protein (CHOP) was performed. Glucose-regulated protein 78 (GRP78), CHOP, and caspase 12 expressions by myocardial tissues and cleaved caspase 12 and p-eIF2 alpha expressions by H9c2 cells were detected with Western blotting. The results showed that methionine overload induced HHcy, resulting in a marked cardiomyocytic ER stress, whereas endogenous production of H2S was reduced in rats with HHcy. H2S supplementation, however, decreased expressions of ER stress associated proteins, including GRP78, CHOP, and caspase 12, by myocardial tissues in vivo. The inhibition of endogenous H2S production further enhanced cardiomyocytic ER stress, but H2S supplementation effectively antagonized the H9c2 cell CHOP, cleaved caspase 12 and p-eIF2a expressions induced by Hcy, thapsigargin, or tunicamycin in vitro. The results suggest that H2S can attenuate cardiomyocytic ER stress in HHcy-induced cardiomyocytic injury. Antioxid. Redox Signal. 12, 1079-1091.