Involvement of p38 MAP kinase pathway in the synergistic activation of PACAP mRNA expression by NGF and PACAP in PC12h cells

Y Sakai; H Hashimoto; N Shintani; S Tomimoto; K Tanaka; A Ichibori; M Hirose; A Baba

doi:10.1006/bbrc.2001.5244

Involvement of p38 MAP kinase pathway in the synergistic activation of PACAP mRNA expression by NGF and PACAP in PC12h cells

Biochem Biophys Res Commun. 2001 Jul 20;285(3):656-61. doi: 10.1006/bbrc.2001.5244.

Authors

Y Sakai¹, H Hashimoto, N Shintani, S Tomimoto, K Tanaka, A Ichibori, M Hirose, A Baba

Affiliation

¹ Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.

PMID: 11453643
DOI: 10.1006/bbrc.2001.5244

Abstract

We have recently shown that in PC12 cells, PACAP and NGF synergistically increase PACAP gene transcription and mRNA level, and that the MAPK/ERK kinase inhibitor PD98059 blocks the PACAP mRNA expression induced by either PACAP or NGF, but not that induced by the combination, suggesting involvement of multiple signaling pathways. Here we show that the p38 MAPK inhibitor SB203580 almost completely inhibits the PACAP mRNA expression induced by PACAP alone or in combination with NGF. PACAP induces neurite outgrowth and potentiates NGF-induced neurite outgrowth in PC12h cells. Unlike the case for the PACAP mRNA expression, SB203580 did not affect, but PD98059 reduced, PACAP and NGF-induced neurite outgrowth. These results indicate that PACAP receptors are coupled to the p38 signaling pathway, and that p38 plays a key role in the regulation of PACAP gene expression, while ERK, but not p38, MAPK is involved in PACAP and NGF-induced neurite outgrowth.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dose-Response Relationship, Drug
Drug Synergism
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Gene Expression / drug effects
Imidazoles / pharmacology
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism*
Nerve Growth Factor / pharmacology*
Neurites / drug effects
Neuropeptides / genetics
Neuropeptides / metabolism*
Neuropeptides / pharmacology*
PC12 Cells
Pituitary Adenylate Cyclase-Activating Polypeptide
Pyridines / pharmacology
RNA, Messenger / biosynthesis*
Rats
Signal Transduction / drug effects
Signal Transduction / physiology
p38 Mitogen-Activated Protein Kinases

Substances

Adcyap1 protein, rat
Enzyme Inhibitors
Flavonoids
Imidazoles
Neuropeptides
Pituitary Adenylate Cyclase-Activating Polypeptide
Pyridines
RNA, Messenger
Nerve Growth Factor
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one