Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia.
OBJECTIVE
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 alphaII-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 mu-calpain activity. Moreover, taurine significantly increased the MAP-2 and alphaII-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.
Sun
Ming
M
Department of Neurochemistry, Beijing Neurosurgical Institute, 6 Tiantan Xi Li, 100050 Beijing, PR China.
Xu
Chao
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism* / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000378:metabolism
D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; C422208:Sptan1 protein, rat; D033921:Vesicular Transport Proteins; D013654:Taurine; C033668:calpastatin; D002154:Calpain; D053148:Caspase 3
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