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 235

translocates from the cytosol to the mitochondria after brain ischemia and causes
release of cytochrome C which in turn activates caspase-3 (Sun et al. 2011 ) .
Caspase-3 is believed to be at the final stage of apoptosis. These results demonstrate
that taurine can prevent the activation of caspase-3 by increasing the ratio of Bcl-2
to Bax in the core of the infarct in MCAO rats by more than fourfold (Fig. 23.4a, b ).
To determine the effect of taurine on apoptosis induced by ER stress, we measured
the expression of CHOP by Western blot analysis in primary neuronal cultures after
hypoxia/reoxygenation and in the MCAO stroke model. As shown in Fig. 23.4c , the
expression of CHOP was upregulated after exposure to hypoxia/reoxygenation.
Western blot analysis showed that taurine can decrease the levels of CHOP both
in vitro in primary neuronal culture and in vivo in the MCAO stroke model
(Fig. 23.4c, d ). Taurine also significantly reduced the expression of caspase-12 and
cleaved caspase-12 in vitro, demonstrating that taurine has the ability to inhibit the
apoptosis induced by ER stress in hypoxia/reoxygenation (Fig. 23.4e ).

23.4 Discussion

In the present study, the potential neuroprotective effects of taurine in an in vitro
experimental model of brain ischemia/reperfusion and an in vivo model of MCAO
stroke in rat were investigated. The main goal of this study was to investigate the
effects of taurine on ER stress pathways in both the core of the brain infarct after
MCAO and in primary neuronal cell culture after hypoxia/reoxygenation. We showed
that taurine can not only protect primary neuronal cultures under hypoxia/reoxygen-
ation conditions in a dose-dependent manner but also downregulate some ER stress
and apoptotic markers in the brain in vivo after MCAO. Taurine as a neurotransmitter,
neuromodulator, membrane stabilizer, and major intracellular free amino acid is
employed in experimental therapies against neuronal damage, hypoxia, and epilepsy
(Birdsall 1998 ). It has been shown that during cerebral ischemia, taurine may exert its
neuroprotective function through both extracellular mechanisms by inhibiting cal-
cium influx and intracellular mechanisms by protecting the mitochondrion through
preventing mitochondrial dysfunction resulting from cytoplasmic calcium overload
(El Idrissi and Trenkner 2004 ; Foos and Wu 2002 ; El Idrissi 2008 ; Huxtable 1992 ) .
Other functions of taurine, such as its role as an antioxidant, an osmoregulator, or an
anti-inflammatory, contribute to its neuroprotective action (Huxtable 1992 ) . During
stroke, the levels of taurine in the extracellular fluid increases (Lo et al. 1998 ) .
The increases in the extracellular taurine levels under brain ischemia may constitute
an important endogenous protective mechanism against neuronal damage (Saransaari
and Oja 2000 ). However, intracellular taurine may be depleted resulting a disruption
of intracellular homeostasis, leading to neuronal damage (Michalk et al. 1997 ;
Huxtable 1992 ). Therefore, exogenous administration of taurine after brain ischemia
may contribute to the recovery from ischemic damage by reducing the release of tau-
rine, thus contributing to the restoration of intracellular homeostasis and the reduction
of ischemic damage through both extracellular and intracellular mechanisms.