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Protective functions of taurine against experimental stroke through depressing mitochondria-mediated cell death in rats

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Abstract

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.

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Abbreviations

ac-DEVD-AFC:

N-acetyl-Asp-Glu-Val-Asp-7-amino-4-trifluoromethylcoumarin

COX IV:

Cytochrome C oxidase subunit IV isoform

DTT:

Dithiothreitol

EDTA:

Ethylenediaminetetraacetic acid

EGTA:

Ethyleneglycol bis(2-aminoethyl ether)tetraacetic acid

HE staining:

Hematoxylin eosin staining

HEPES:

N-2-hydroxyethylpiperazine-N′-2′-ethanesulfonic acid

MCAo:

Middle cerebral artery occlusion

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

TTC:

2,3,5-Triphenyltetrazolium chlorides

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling

NBT/BCIP:

Nitroblue tetrazolium/5-bromo-4-chloro-3-inoloyl-phosphate

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurochemistry, Beijing Neurosurgical Institute, 6 Tiantan Xili, Chongwen District, Beijing, 100050, China

    Ming Sun, Yi Gu, Yumei Zhao & Chao Xu

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  1. Ming Sun
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  2. Yi Gu
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  3. Yumei Zhao
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  4. Chao Xu
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Correspondence to Chao Xu.

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Sun, M., Gu, Y., Zhao, Y. et al. Protective functions of taurine against experimental stroke through depressing mitochondria-mediated cell death in rats. Amino Acids 40, 1419–1429 (2011). https://doi.org/10.1007/s00726-010-0751-8

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  • DOI: https://doi.org/10.1007/s00726-010-0751-8

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