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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

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Taurine 8

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 776))

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.

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Abbreviations

ER:

Endoplasmic reticulum

MCAO:

Middle cerebral artery occlusion

GRP78:

Glucose-regulated protein 78

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Authors and Affiliations

  1. Department of Biomedical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA

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

  2. Centre of Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, FL, 33431, USA

    Jigar Modi, Howard Prentice & Jang-Yen Wu

  3. Department of Neurology and Sleep Center, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan

    Po-Chih Chen

  4. Program in Integrative Biology, Florida Atlantic University, Boca Raton, FL, 33431, USA

    Rui Tao, Howard Prentice & Jang-Yen Wu

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  1. Payam Mohammad Gharibani
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  2. Jigar Modi
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  3. Chunliu Pan
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  4. Janet Menzie
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  8. Howard Prentice
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  9. Jang-Yen Wu
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Correspondence to Payam Mohammad Gharibani , Rui Tao , Howard Prentice or Jang-Yen Wu .

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  1. City University of New York, Center for Developmental Neuroscience, College of Staten Island, 2800 Victory Blvd, Staten Island, 10314, New York, USA

    Abdeslem El Idrissi

  2. City University of New York, Department of Biology, College of Staten Island, Victory Blvd 2800, Staten Island, 10314, New York, USA

    William J. L'Amoreaux

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Gharibani, P.M. et al. (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: El Idrissi, A., L'Amoreaux, W. (eds) Taurine 8. Advances in Experimental Medicine and Biology, vol 776. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6093-0_23

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