Protective functions of taurine against experimental stroke through depressing mitochondria-mediated cell death in rats.
Taurine, an abundant amino acid in the nervous system, is reported to reduce ischemic brain injury in a dose-dependent manner. This study was designed to investigate whether taurine protected brain against experimental stroke through affecting mitochondria-mediated cell death pathway. Rats were subjected to 2-h ischemia by intraluminal filament, and then reperfused for 22 h. It was confirmed again that taurine (50 mg/kg) administered intravenously 1 h after ischemia markedly improved neurological function and decreased infarct volume at 22 h after reperfusion. In vehicle-treated rats, the levels of intracellular ATP and the levels of cytosolic and mitochondrial Bcl-xL in the penumbra and core were markedly reduced, while the levels of cytosolic Bax in the core and mitochondrial Bax in the penumbra and core were enhanced significantly. There was a decrease in cytochrome C in mitochondria and an increase in cytochrome C in the cytosol of the penumbra and core. These changes were reversed by taurine. Furthermore, taurine inhibited the activation of calpain and caspase-3, reduced the degradation of αII-spectrin, and attenuated the necrotic and apoptotic cell death in the penumbra and core. These data demonstrated that preserving the mitochondrial function and blocking the mitochondria-mediated cell death pathway may be one mechanism of taurine's action against brain ischemia.
Sun
Ming
M
Department of Neurochemistry, Beijing Neurosurgical Institute, 6 Tiantan Xili, Chongwen District, Beijing, China.
Gu
Yi
Y
Zhao
Yumei
Y
Xu
Chao
C
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013654:Taurine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494828:Bax protein, rat; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D013654:Taurine; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D002154:Calpain; D053148:Caspase 3