The mechanism of taurine protection against endoplasmic reticulum stress in an animal stroke model of cerebral artery occlusion and stroke-related conditions in primary neuronal cell culture

Payam Mohammad Gharibani, Jigar Modi, Chunliu Pan, Janet Menzie, Zhiyuan Ma, Po Chih Chen, Rui Tao, Howard Prentice, Jang Yen Wu

研究成果: 書貢獻/報告類型章節

41 引文 斯高帕斯(Scopus)

摘要

Taurine is an inhibitory neurotransmitter and is one of the most abundant amino acids present in the mammalian nervous system. Taurine has been shown to provide protection against neurological diseases, such as Huntington's disease, Alzheimer's disease, and stroke. Ischemic stroke is one of the leading causes of death and disability in the world. It is generally believed that ischemia-induced brain injury is largely due to excessive release of glutamate resulting in excitotoxicity and cell death. Despite extensive research, there are still no effective interventions for stroke. Recently, we have shown that taurine can provide effective protection against endoplasmic reticulum (ER) stress induced by excitotoxicity or oxidative stress in PC12 cell line or primary neuronal cell cultures. In this study, we employed hypoxia/reoxygenation conditions for primary cortical neuronal cell cultures as an in vitro model of stroke as well as the in vivo model of rat focal middle cerebral artery occlusion (MCAO). Our data showed that when primary neuronal cultures were first subjected to hypoxic conditions (0.3%, 24 h) followed by reoxygenation (21%, 24-48 h), the cell viability was greatly reduced. In the animal model of stroke (MCAO), we found that 2 h ischemia followed by 4 days reperfusion resulted in an infarct of 47.42 ± 9.86% in sections 6 mm from the frontal pole. Using taurine greatly increased cell viability in primary neuronal cell culture and decreased the infarct area of sections at 6 mm to 26.76 ± 6.91% in the MCAO model. Furthermore, levels of the ER stress protein markers GRP78, caspase-12, CHOP, and p-IRE-1 which were markedly increased in both the in vitro and in vivo models significantly declined after taurine administration, suggesting that taurine may exert neuroprotection functions in both models. Moreover, taurine could downregulate the ratio of cleaved ATF6 and full-length ATF6 in both models. In the animal model of stroke, taurine induced an upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 protein activity indicating that it attenuates apoptosis in the core of the ischemic infarct. Our results show not only taurine elicits neuroprotection through the activation of the ATF6 and the IRE1 pathways, but also it can reduce apoptosis in these models.

原文英語
主出版物標題Taurine 8
主出版物子標題Volume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation
發行者Springer New York LLC
頁面241-258
頁數18
ISBN(列印)9781461460923
DOIs
出版狀態已發佈 - 2013

出版系列

名字Advances in Experimental Medicine and Biology
776
ISSN(列印)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Gharibani, P. M., Modi, J., Pan, C., Menzie, J., Ma, Z., Chen, P. C., Tao, R., Prentice, H., & Wu, J. Y. (2013). The mechanism of taurine protection against endoplasmic reticulum stress in an animal stroke model of cerebral artery occlusion and stroke-related conditions in primary neuronal cell culture. 於 Taurine 8: Volume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation (頁 241-258). (Advances in Experimental Medicine and Biology; 卷 776). Springer New York LLC. https://doi.org/10.1007/978-1-4614-6093-0_23