“
“We previously reported that cells harboring the hepatitis C virus (HCV) RNA replicon as well as those expressing HCV NS3/4A exhibited increased sensitivity to suboptimal doses of apoptotic stimuli to undergo mitochondrion-mediated apoptosis (Y. Nomura-Takigawa, et al., J. Gen. Virol. 87: 1935-1945, 2006). Little is known, however, about whether or not HCV infection induces apoptosis of the virus-infected cells. In this study, by using the chimeric J6/JFH1 strain of HCV genotype 2a,we demonstrated that HCV infection induced cell death in Huh7.5 cells. The cell death was associated with activation of caspase 3, nuclear translocation

of activated caspase 3, and cleavage of DNA repair enzyme poly(ADP-ribose) polymerase, which is known to be an important substrate for activated caspase 3. These results suggest that HCV-induced cell death is, in PD173074 fact, apoptosis. Moreover, HCV infection activated Bax,

a proapoptotic member of the Bcl-2 family, as revealed by its conformational change and its increased accumulation on mitochondrial membranes. Concomitantly, HCV infection induced disruption of mitochondrial transmembrane potential, followed by mitochondrial swelling and release of cytochrome c from mitochondria. HCV infection also caused oxidative stress via increased production AZD8186 supplier of mitochondrial superoxide. selleck chemicals llc On the other hand, HCV infection did not mediate increased expression of glucose-regulated protein 78 (GRP78) or GRP94, which are known as endoplasmic reticulum (ER) stress-induced proteins; this result suggests that ER stress is not primarily involved in HCV-induced apoptosis in our experimental system. Taken together, our present results suggest that HCV infection induces apoptosis of the host cell through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway(s).”
“Glutamate is a major excitatory neurotransmitter in the CNS that is involved in numerous cellular

functions, including cell death and survival. Metabotropic glutamate receptors (mGluR) are G-protein coupled receptors that have been classified into three groups on the basis of signal transduction pathways and pharmacological profiles. Group I, II, and III mGluRs are found on cell types within and peripheral to the CNS, including neurons, microglia, astrocytes, oligodendrocytes, T- and B-cell lymphocytes, osteoblasts, hepatocytes, and endothelial cells, among others. These receptors have a number of effects on cells that can influence outcome after trauma, including reducing neuronal and oligodendroglial cell death, inflammation, and endothelial permeability. Thus, mGluRs are a promising multipotential therapeutic approach.