Neuroprotective Mechanism of Taurine due to Up-regulating Calpastatin and Down-regulating Calpain and Caspase-3 during Focal Cerebral Ischemia |
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Authors: | Ming Sun Chao Xu |
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Institution: | (1) Department of Neurochemistry, Beijing Neurosurgical Institute, 6 Tiantan Xi Li, 100050 Beijing, P.R. China |
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Abstract: | 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. |
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Keywords: | Focal cerebral ischemia Taurine Calpastatin Calpain Caspase-3 Apoptosis Neuroprotection |
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