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

来源：

Cellular and Molecular Neurobiology | 2008年 / 28卷 / 4期

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

页码：593 / 611

页数：18

共 71 条

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