Hepatitis C virus core protein promotes the migration and invasion of hepatocyte via activating transcription of extracellular matrix metalloproteinase inducer.

The chronic infection of hepatitis C virus (HCV) becomes a main factor evoking hepatocellular carcinoma, where the HCV core protein plays a central role in hepatocarcinogenesis. Whether the core protein directly contributes to metastasis of hepatocytes still remains to be reported in literature. Transwell chamber migration assay, Boyden chamber invasion assays and scanning electron microscopy observations were performed to determine the prometastatic ability of HCV core protein when expressed in human hepatocyte L02 cells. In addition, western blots, dual-luciferase assays, and chromatin immunoprecipitation assays were used to elucidate HCV core protein dependent pathways that promote metastasis in hepatocytes. Our investigation suggests that HCV core protein markedly enhances the capability of migration and invasion in L02 clones expressing HCV core proteins. The metastasis-promoting effect of the core protein is, in part, highly dependent on its effect on promoting the binding of transcription factor Sp1 to the extracellular matrix metalloproteinase inducer promoter. The effect of Sp1 binding resulted in an increase in extracellular matrix metalloproteinase inducer expression and progression of metastasis. Thus, we report that the expression of HCV core protein contributes to the metastasis of hepatocyte cells through activating transcription of extracellular metalloproteinase inducer.

Ketamine blocks non-N-methyl-D-aspartate receptor channels attenuating glutamatergic transmission in the auditory cortex.

OBJECTIVE: To investigate the influence of ketamine on non-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the auditory cortex. MATERIAL AND METHODS: Using whole-cell patch-clamp techniques on pyramidal neurons, we studied the effects of ketamine on excitatory post-synaptic potentials (EPSPs) evoked by electrical stimulation of internal capsule fibers in slices of gerbil auditory cortex. RESULTS: After blockade of the slow, NMDA receptor-mediated EPSP component with DL-2-amino-5-phosphonovaleric acid, application of ketamine in a concentration-dependent manner led to a reduction in the amplitude of fast, 6-cyano-7-nitroquinoxalinedione (CNQX)-sensitive EPSPs, accompanied by an increased membrane resistance. Blockade of non-NMDA glutamate receptors with CNQX prevented both effects. CONCLUSION: Ketamine reduces membrane conductance and glutamatergic excitation, in part by blocking alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor channels that may be constitutively active at a low level in slice preparations of auditory cortex.