Nerve growth factor-induced up-regulation of cytosolic phospholipase A2α level in rat PC12 cells

Nerve growth factor (NGF) regulates various types of gene transcription in neurons. One of the cytosolic phospholipase A(2)s, cPLA(2)alpha, 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(2)alpha expression and its signaling pathways in PC 12 cells, which differentiate into neuronal-like cells with neurites by NGF treatment. Treatment with NGF increased cPLA(2)alpha mRNA level after 4 h and its protein level 24 h after NGF addition. The NGF-induced increase in cPLA(2)alpha 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(2)alpha mRNA and its protein) were inhibited by selective inhibitors for the ERK1/2 pathway, p38 MAPK and c-Jun NH2-terminal kinase. Epidermal growth factor, which transiently activates ERK1/2, did not modify cPLA(2)alpha expression. Although phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), alone showed no effect, NGF-induced cPLA(2)alpha mRNA expression decreased due to the inhibition of PKC. These findings suggest that NGF-induced cPLA(2)alpha expression is regulated by gene transcription via the ERK1/2, p38 MAPK and PKC pathways in PC12 cells. (C) 2004 Elsevier Ireland Ltd. All rights reserved.