Taurine prevents the decrease in expression and secretion of extracellular superoxide dismutase induced by homocysteine - Amelioration of homocysteine-induced endoplasmic reticulum stress by taurine

Article

关键词: ENDOTHELIAL-CELL INJURY;    CARDIOVASCULAR-DISEASE;    PROTEIN-KINASES;    NITRIC-OXIDE;    ATHEROSCLEROSIS;    MECHANISM;    HOMOCYST(E)INE;    HYPERTENSION;    ACCUMULATION;    ACTIVATION;   

DOI  :  10.1161/hc3601.093976

来源: SCIE

【 摘 要 】

Background-Hyperhomocysteinemia is an independent risk factor for atherosclerosis. Homocysteine has been shown to induce endoplasmic reticulum (BR) stress in vascular endothelial cells. ER stress is a condition in which glycoprotein trafficking is disrupted and unfolded proteins accumulate in the ER. ER molecular chaperons, such as GRP78, are induced and an ER resident kinase, PERK, is activated when cells are subjected to ER stress. Conversely, taurine is reported to have antiatherogenic effects by unknown mechanisms. To elucidate the mechanisms by which homocysteine induces atherosclerosis and taurine prevents it, we examined whether homocysteine and taurine affect the expression and secretion of extracellular superoxide dismutase (EC-SOD), a glycoprotein secreted from vascular smooth muscle cells (VSMCs) that protects the vascular wall from oxidative stress. Methods and Results-We assessed the expression of EC-SOD and GRP78 mRNA in cultured rat VSMCs by Northern blot analysis. The EC-SOD protein secreted into the culture medium was examined by Western blot analysis. Homocysteine (5 mmol/L) and other ER stress inducers, including A23187, were found to decrease EC-SOD mRNA expression and protein secretion. Furthermore, they upregulated GRP78 mRNA expression and activated PERK. Taurine (0.5 to 10 mmol/L), conversely, prevented these actions induced by homocysteine. Conclusions-Homocysteine induces ER stress and reduces the secretion and expression of EC-SOD in VSMCs, leading to increased oxidative stress in the vascular wall. Taurine restores the secretion and expression of EC-SOD by ameliorating ER stress induced by homocysteine.

【 授权许可】

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