Modification of redox processes in astroglial cells induced by microbial and viral infections.

BACKGROUND: The authors hypothesized that the cell redox state might be modified during microbial and viral infections. To detect and evaluate changes in astroglial cell redox state, rat C6 glioma cells after exposure to lipopolysaccharide (LPS) or after herpes simplex virus type 1 (HSV-1) inoculation were used. Redox state modification of glioma cells was determined by the change in menadione-induced superoxide yield. MATERIAL/METHODS: Menadione-induced superoxide formation was registered by the lucigenin-enhanced chemiluminescence (CL) method. RESULTS: The results demonstrate that exposure of C6 glioma cells to LPS for 24 hours resulted in a dose-dependent increase in the mitotic index and integral intensity of menadione-induced lucigenin-enhanced CL. Menadione-induced ROS generation in C6 cells during HSV-1 infection changed depending on the time after HSV-1 inoculation. CONCLUSIONS: The redox state of astroglial cells is modified during microbial and viral infections. The use of redox-active quinones is an informative model for determining cell redox state change and analyzing cells' functional state.

Effects of peroxynitrite and lipopolysaccharide on mitotic activity of C6 glioma cells.

Peroxynitrite is one of the most potent neurotoxic agents with multiple targets in neurons and glial cells. This study addressed a question of whether peroxynitrite-mediated cytotoxicity can be prevented by Escherichia coli lypopolisaccharide (LPS) due to its mitogenic activity towards C6 glioma cells. A number of characteristic morphological changes (processes impairments, nuclei modifications, cytoplasm vacuolization) and apoptotic cells were observed in the cell culture after 24-h treatment with 3-morpholinosyndnonimine (SIN-1), a well-known donor of peroxynitrite. These morphological changes were clearly associated with a SIN-1 dose-dependent increase in the number of pathological mitoses as well as with SIN-1 inhibition of the menadione-induced, lucigenin-enhanced chemiluminescence of C6 glioma cells, an independent indicator of mitotic activity of these cells. The mitotic index of C6 glioma cells increased in response to LPS and underwent non-uniform changes depending on SIN-1 concentrations. At a mitogenic concentration of 100 ng/ml, LPS reduced significantly the toxicity of SIN-1 determined as the accumulation of pathological mitoses, thus acting as a protective agent. Taken together, our findings indicate that SIN-1 specifically impairs the mitotic process in C6 glioma cells, and provide the first evidence that antimitotic effects of peroxynitrite can be restored by LPS.