Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia

被引:70
作者
Ming Sun [1 ]
Chao Xu [1 ]
机构
[1] Department of Neurochemistry, Beijing Neurosurgical Institute, Beijing 100050
关键词
Apoptosis; Calpain; Calpastatin; Caspase-3; Focal cerebral ischemia; Neuroprotection; Taurine;
D O I
10.1007/s10571-007-9183-8
中图分类号
学科分类号
摘要
Aims: Taurine as an endogenous substance possesses a number of cytoprotective properties. In the study, we have evaluated the neuroprotective effect of taurine and investigated whether taurine exerted neuroprotection through affecting calpain/calpastatin or caspase-3 actions during focal cerebral ischemia, since calpain and caspase-3 play central roles in ischemic neuronal death. Methods: Male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion (MCAo), and 22 h of reperfusion. Taurine was administrated intravenously 1 h after MCAo. The dose-responses of taurine to MCAo were determined. Next, the effects of taurine on the activities of calpain, calpastatin and caspase-3, the levels of calpastatin, microtubule-associated protein-2 (MAP-2) and αII-spectrin, and the apoptotic cell death in penumbra were evaluated. Results: Taurine reduced neurological deficits and decreased the infarct volume 24 h after MCAo in a dose-dependent manner. Treatment with 50 mg/kg of taurine significantly increased the calpastatin protein levels and activities, and markedly reduced the m-calpain and caspase-3 activities in penumbra 24 h after MCAo, however, it had no significant effect on μ-calpain activity. Moreover, taurine significantly increased the MAP-2 and αII-spectrin protein levels, and markedly reduced the ischemia-induced TUNEL staining positive score within penumbra 24 h after MCAo. Conclusions: Our data demonstrate the dose-dependent neuroprotection of taurine against transient focal cerebral ischemia, and suggest that one of protective mechanisms of taurine against ischemia may be blocking the m-calpain and caspase-3-mediated apoptotic cell death pathways. © 2007 Springer Science+Business Media, LLC.
引用
收藏
页码:593 / 611
页数:18
相关论文
共 71 条
[71]  
Yoshida K., Yamasaki Y., Kawashima S., Calpain activity alters in rat myocardial subfractions after ischemia or reperfusion, Biochim Biophys Acta, 1182, pp. 215-220, (1993)