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 - Advances in Experimental Medicine and Biology - page 226

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 administra-
tion, 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.

Abbreviations

ER Endoplasmic reticulum

MCAO Middle cerebral artery occlusion

GRP78 Glucose-regulated protein 78

23.1 Introduction

The endoplasmic reticulum (ER) is an important subcellular organelle that is
responsible for intracellular calcium homeostasis, protein secretion, and lipid
biosynthesis (Ma and Hendershot 2004 ; Anelli and Sitia 2008 ). ER stress plays a

R. Tao ( * )
Department of Biomedical Sciences , Charles E. Schmidt College
of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA
Program in Integrative Biology, Florida Atlantic University,
Boca Raton , FL 33431 , USA
e-mail: [e-mail]
H. Prentice ( * ) ￿ J.-Y. Wu ( * )
Department of Biomedical Sciences , Charles E. Schmidt College
of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA
Program in Integrative Biology, Florida Atlantic University,
Boca Raton , FL 33431 , USA
Centre of Complex Systems and Brain Sciences, Florida Atlantic University,
Boca Raton , FL 33431 , USA
e-mail: [e-mail] ; [e-mail]