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 237

In this chapter, levels of cell viability as measured by the ATP assay were
significantly enhanced by taurine after hypoxia/reoxygenation treatment, confirming
the protective role of taurine. On the other hand, TTC results showed that posttreat-
ment with taurine after MCAO could decrease the volume of cerebral damage,
although this effect was not as strong as that of taurine pretreatment (Sun and Xu
2008 ; Sun et al. 2011 ). TTC staining clearly shows the stroke region which allows
one to determine the exact size of cerebral infarction as well as to distinguish
between the core of the infarct area, the penumbra, and healthy brain tissue (Benedek
et al. 2006 ). Our data showed that using taurine (40 mg/kg), 24 h after reperfusion
can still decrease lesion volume after 4 days. The colorless TTC is enzymatically
reduced to a red formazan product by endogenous dehydrogenase enzyme com-
plexes which are most abundant in mitochondria. Our ATP assay and TTC data
confirm previous reports showing that taurine can regulate mitochondrial protein
synthesis, enhance electron transport chain activity, and thereby increase the ATP
levels and protect against excessive toxic superoxide generation (Schaffer et al.
2009 ; Jong et al. 2011 ). As a neuroprotective agent, taurine must pass through the
blood-brain barrier (BBB) and enter into the brain under neuropathological condi-
tions. On one hand, there are some reports of increases in radioactive taurine uptake
in brain after systemic administration of radiolabeled taurine (Pasantes-Morales and
Arzate 1981 ; Urquhart et al. 1974 ); on the other hand, in neuropathological condi-
tions, the BBB may be ruptured and drugs can pass more freely. Moreover, taurine
has been used with varying degrees of success in clinical therapy for epilepsy and
other seizure disorders, and these data provide supporting evidence that taurine will
cross the BBB and reach the damaged area when it is administrated subcutaneously
after MCAO.
It is believed that brain ischemia followed by glutamate excitotoxicity leads to
intracellular calcium overload and initiates a series of intracellular events, such as
the release of apoptotic proteins leading to necrotic and apoptotic cell death (Nakka
et al. 2008 ; Lipton 1999 ). Some reports have demonstrated that taurine can regulate
intracellular calcium homeostasis through enhancing mitochondrial function, reduc-
ing the release of calcium from intracellular storage pools, and increasing the capac-
ity of mitochondria to sequester calcium (Foos and Wu 2002 ; El Idrissi 2008 ; El
Idrissi and Trenkner 2004 ). These data suggest that inhibiting intracellular calcium
overload may be essential for the protection of taurine against MCAO. Taurine may
block caspase-3 by regulating the release of mitochondrial cytochrome
C. Cytochrome C release is regulated by the BCL-2 protein family of apoptotic
regulators (Juin 1998 ). During brain ischemia, Bax expression is increased, and Bax
protein translocates to mitochondria to induce cytochrome C release (Schäbitz et al.
2003 ; Gao and Dou 2000 ). We showed that 4 days after MCAO, taurine could
decrease Bax protein expression, while Bcl-2 protein expression increased. Thus
regulation of Bcl-2 and Bax has been demonstrated in our results, although the
effect of taurine on intracellular calcium has not been directly investigated in this
study. A high ratio of Bcl-2 to Bax can prevent release cytochrome C from mito-
chondria which results in decreased caspase-3 activity. As we showed in vitro in
primary neuronal cultures, the proapoptotic factor CHOP is expressed at low levels