Inhibition of thioredoxin-1 with siRNA exacerbates apoptosis by activating the ASK1-JNK/p38 pathway in brain of a stroke model rats.

Inhibition of thioredoxin-1 with siRNA exacerbates apoptosis by activating the ASK1-JNK/p38 pathway in brain of a stroke model rats.
Brain Res. 2014 Dec 22;
Authors: Wu X, Li L, Zhang L, Wu J, Zhou Y, Zhou Y, Zhao Y, Zhao J
Abstract
Apoptosis is critical for the development of cerebral ischemia/reperfusion injury. Thioredoxin-1(Trx-1) protein has been reported to have anti-apoptotic effects in a variety of cell types, and it has been implicated in brain injury after middle cerebral artery occlusion (MCAO). Thus, we studied the effects of Trx1 silencing after MCAO in rats and examined whether inhibition of endogenous Trx1 could increase tissue levels of apoptosis. Male Sprague-Dawley rats (N=170) were subjected to 1h of middle cerebral arterial occlusion followed by 24h of reperfusion. Trx1 siRNAs were injected into rat brains 24h prior to MCAO. Then, 24h after MCAO, brains were collected from euthanized rats for investigation. Treatment with Trx1 siRNA significantly increased mortality, behavioral deficits, and cerebral infarction volume and exacerbated neuronal cell apoptotic death after MCAO injury. Western blot revealed increased expression of apoptotic proteins such as P-ASK1, P-JNK, P-p38, cleaved caspase-3 and increased the level of cytochrome c in the cytosolic fraction in the Trx1 siRNA-treated group. Co-immunoprecipitation assay suggested an interaction between Trx1 and ASK1 in normal rat brains and Trx1 siRNA dissociated AS...

Source: Brain Research - December 22, 2014 Category: Neurology Authors: Wu X, Li L, Zhang L, Wu J, Zhou Y, Zhou Y, Zhao Y, Zhao J Tags: Brain Res Source Type: research