Nerve growth factor-induced up-regulation of cytosolic phospholipase A 2α level in rat PC12 cells

Abstract

Nerve growth factor (NGF) regulates various types of gene transcription in neurons. One of the cytosolic phospholipase A 2s, cPLA 2α, which preferentially cleaves phospholipids at the sn-2 position to arachidonic acid (AA), is involved in neuronal responses including survival. We investigated the effect of NGF on cPLA 2α expression and its signaling pathways in PC12 cells, which differentiate into neuronal-like cells with neurites by NGF treatment. Treatment with NGF increased cPLA 2α mRNA level after 4 h and its protein level 24 h after NGF addition. The NGF-induced increase in cPLA 2α mRNA was inhibited by actinomycin D. NGF caused phosphorylation of mitogen-activated protein kinases (MAPKs); sustained phosphorylation of extracellular-regulated kinases (ERK1/2) and transient phosphorylation of p38 MAPK. NGF responses (cPLA 2α mRNA and its protein) were inhibited by selective inhibitors for the ERK1/2 pathway, p38 MAPK and c-Jun NH 2-terminal kinase. Epidermal growth factor, which transiently activates ERK1/2, did not modify cPLA 2α expression. Although phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), alone showed no effect, NGF-induced cPLA 2α mRNA expression decreased due to the inhibition of PKC. These findings suggest that NGF-induced cPLA 2α expression is regulated by gene transcription via the ERK1/2, p38 MAPK and PKC pathways in PC12 cells.