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

Background-Hyperhomocysteinemia is an independent risk factor for atheroscl erosis. Homocysteine has been shown to induce endoplasmic reticulum (BR) st ress in vascular endothelial cells. ER stress is a condition in which glyco protein trafficking is disrupted and unfolded proteins accumulate in the ER . ER molecular chaperons, such as GRP78, are induced and an ER resident kin ase, 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 a nd 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 p rotects 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 i nto the culture medium was examined by Western blot analysis. Homocysteine (5 mmol/L) and other ER stress inducers, including A23187, were found to de crease EC-SOD mRNA expression and protein secretion. Furthermore, they upre gulated 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 ex pression of EC-SOD in VSMCs, leading to increased oxidative stress in the v ascular wall. Taurine restores the secretion and expression of EC-SOD by am eliorating ER stress induced by homocysteine.