ROLE OF PARP-1 AND PARP-2 IN CELL DEATH AND MODULATION OF THEIR EXPRESSION BY NEUROPROTECTIVE AGENTS IN PRIMARY RAT ASTROCYTES AND OLIGODENDROCYTES

PARPs play an important role in cell cycle regulation, genome stability, apoptotic cell death. Seventeen PARP family members have been identified, with PARP-1 and PARP-2 sharing the highest homology (69%). We examined the effects of L-carnosine and trehalose on PARP-1 and PARP-2 expression through PCR and Western analysis, in primary rat astroglial and oligodentrocyte cells, treated with lipopolysaccharide (LPS) and interferon gamma (INFγ) to induce stress conditions with or without carnosine or trehalose. After 24 h of LPS and INF-γ treatment, we observed an increase of nitrite production and LDH release and a decrease of cell viability (MTT). Carnosine or trehalose treatment decreased nitrite and LDH release and increased cell viability. Due to the NO binding activity of carnosine, such effect is attributable to a down-regulation of PARP-1 and PARP-2 expression by carnosine and trehalose treatment under stress conditions. These data suggest that besides their antioxidant role, carnosine and trehalose may also modify the pathways regulated by PARPs. To further verify our hypothesis we are investigating the role of these molecules in neurodegenerative disorders.