Nerve growth factor-induced up-regulation of cytosolic phospholipase A2alpha 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 PC12 cells, which differentiate into neuronal-like cells with neurites by NGF treatment. Treatment with NGF increased cPLA(2)alpha mRNA level after 4h and its protein level 24h 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 NH(2)-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.
Akiyama
Nobuteru
N
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Hatori
Yoshio
Y
Takashiro
Yuko
Y
Hirabayashi
Tetsuya
T
Saito
Takeshi
T
Murayama
Toshihiko
T
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D054513:Group IV Phospholipases A2; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000502:physiology*; D016716:PC12 Cells; D010741:Phospholipases A / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D012333:RNA, Messenger; D020932:Nerve Growth Factor; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054513:Group IV Phospholipases A2