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 231

23.2.3 Data Expression and Statistical Analysis

All data were expressed as the mean ± SEM. The statistical significance of the data
was determined with t -test or one-way ANOVA combined with Dunnett post hoc or
Tukey test for comparison between groups.

23.3 Results

23.3.1 Primary Neuronal Culture Viability and Percent Area

of Ischemic Injury in Rat Brain

Our data showed that different concentrations of taurine can attenuate cell death in
hypoxia/reoxygenation. In order to determine the appropriate concentration of tau-
rine in cultures, cortical neurons were exposed to hypoxia and reoxygenation in the
presence of 1, 5, and 10 mM taurine as shown in Fig. 23.1b . After hypoxia and
reoxygenation, viability of neurons without taurine treatment dropped to approxi-
mately 49% of control. Taurine treatment dramatically increased the cell viability.
The presence of 1 mM taurine substantially increased the cell viability to greater
than 70% of the control level. When taurine concentration was increased to 10 mM,
cell viability was further enhanced to 85% of the control.
In the rat MCAO stroke experiments, representative coronal brain sections from
the control group (MCAO vehicle-treated) and experimental group (MCAO taurine-
treated) stained with 1% TTC are shown in Fig. 23.1c . Four days of reperfusion
following 2 h of ischemia resulted in an infarct of 47.42 ± 9.86% in the control
group. Although in all sections the infarct volume was decreased in the taurine-
treated group versus vehicle-treated group, only in sections 6 mm from the anterior
pole (infarct volume of 26.76 ± 6.91%) was the difference significant ( p < 0.05). The
sham-operated group showed no ischemic injury as determined by TTC staining.

23.3.2 The ATF6 and IRE1 Pathways Were Inhibited by Taurine,

But There Was No Effect on the PERK Pathway

PERK, ATF6, and IRE1 are the three major ER stress-induced signaling pathways.
Since taurine can downregulate GRP78 in hypoxic conditions in cell culture and in
a stroke model (data not shown), we aimed to further identify which signaling path-
way is involved in the protection. The phosphorylation of elF2a, a downstream
PERK pathway component, specifically regulates the translation of the transcription
factor ATF4, leading to translational attenuation (Szegezdi et al. 2006 ) . ATF4 is
highly expressed after hypoxia/reoxygenation and increased by approximately