Differential expression profiles of PLC-β1 and -δ1 in primary cultured rat cortical neurons treated with N-methyl- d-aspartate and peroxynitrite

Abstract

Phospholipase C (PLC)-δ1 protein appears to accumulate aberrantly in Alzheimer’s disease brains and its expression is reported to be induced by overstimulation of N-methyl- d-aspartate (NMDA) receptor, but there is little knowledge on its physiological role. To clarify this, we examined the expression profile of PLC-δ1 in primary cultured rat cortical neurons treated with NMDA or peroxynitrite, in comparison with those of PLC-β1 and -γ1, the overexpression of both of which protects cells from oxidative stress. Overstimulation of NMDA receptor decreased and increased the expression of PLC-β1 and -δ1, respectively, but did not affect that of PLC-γ1, in the neurons. The viability of neurons decreased depending on the period of treatment with S-nitroso- N-acetyl d, l-penicillamine (SNAP), there being a significant decrease on 9 h treatment. On examination of the expression profiles of PLC isozymes after treatment of neurons with SNAP, PLC-β1 was found to be increased after 1 h treatment and decreased after 9 h treatment, while PLC-δ1 was significantly increased, especially after 5 h treatment. Peroxynitrite treatment caused a dose-dependent decrease in the viability of neurons, and expression of PLC-β1 was increased by a nontoxic level of peroxynitrite and decreased by a toxic level of it, while that of PLC-δ1 was increased by a sublethal level of it. These findings suggested that induction of PLC-β1 might protect neurons from oxidative stress, but that of PLC-δ1 might have the opposite role, although both isozymes responded to oxidative stress.