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

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.

Original languageEnglish (US)
Title of host publicationTaurine 8
Subtitle of host publicationVolume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation
PublisherSpringer New York LLC
Pages241-258
Number of pages18
ISBN (Print)9781461460923
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume776
ISSN (Print)0065-2598

Fingerprint

Endoplasmic Reticulum Stress
Cerebral Arteries
Primary Cell Culture
Taurine
Cell culture
Animals
Animal Models
Stroke
Middle Cerebral Artery Infarction
Cells
Cell Survival
Down-Regulation
Ischemia
Caspase 12
Apoptosis
Oxidative stress
PC12 Cells
Huntington Disease
Neurology
Cell death

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mohammadgharibani, P., Modi, J., Pan, C., Menzie, J., Ma, Z., Chen, P. C., ... 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. In Taurine 8: Volume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation (pp. 241-258). (Advances in Experimental Medicine and Biology; Vol. 776). Springer New York LLC. https://doi.org/10.1007/978-1-4614-6093-0_23

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. / Mohammadgharibani, Payam; Modi, Jigar; Pan, Chunliu; Menzie, Janet; Ma, Zhiyuan; Chen, Po Chih; Tao, Rui; Prentice, Howard; Wu, Jang Yen.

Taurine 8: Volume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation. Springer New York LLC, 2013. p. 241-258 (Advances in Experimental Medicine and Biology; Vol. 776).

Research output: Chapter in Book/Report/Conference proceedingChapter

Mohammadgharibani, P, Modi, J, Pan, C, Menzie, J, Ma, Z, Chen, PC, Tao, R, Prentice, H & Wu, JY 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. in Taurine 8: Volume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation. Advances in Experimental Medicine and Biology, vol. 776, Springer New York LLC, pp. 241-258. https://doi.org/10.1007/978-1-4614-6093-0_23
Mohammadgharibani P, Modi J, Pan C, Menzie J, Ma Z, Chen PC et al. 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. In Taurine 8: Volume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation. Springer New York LLC. 2013. p. 241-258. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-1-4614-6093-0_23
Mohammadgharibani, Payam ; Modi, Jigar ; Pan, Chunliu ; Menzie, Janet ; Ma, Zhiyuan ; Chen, Po Chih ; Tao, Rui ; Prentice, Howard ; Wu, Jang Yen. / 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. Taurine 8: Volume 2: Nutrition and Metabolism, Protective Role, and Role in Reproduction, Development, and Differentiation. Springer New York LLC, 2013. pp. 241-258 (Advances in Experimental Medicine and Biology).
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