title: Calmodulin-dependent activation of p38 and p42/44 mitogen-activated protein kinases contributes to c-fos expression by calcium in PC12 cells: modulation by nitric oxide.
abstract: Calcium and nitric oxide (NO) are important messengers for the activity-dependent immediate-early gene (IEG) expressions in neuronal cells. In the present study, we have investigated the roles of two mitogen-activated protein (MAP) kinases, extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase (p38 kinase) in calcium- and NO-induced c-fos expression in PC12 cells. Membrane depolarization-induced calcium increases activated both ERK and p38 kinase within 5 min. The activation of both ERK and p38 kinase by calcium was a calmodulin-dependent process since the pretreatment of W13 or calmidazolium, specific calmodulin antagonists, blocked calcium-induced activation of both MAP kinases. Calcium-induced c-fos expression was significantly reduced by the pretreatment of either MEK inhibitor (PD98059) or p38 kinase inhibitor (SB203580). This finding indicates that the calmodulin-dependent activation of ERK and p38 kinase is involved in calcium-induced c-fos expression. However, sodium nitroprusside and SIN-1, known to release NO, dose-dependently activated only ERK. NO-induced c-fos expression was partially inhibited by the PD98059. We also observed that NO dose-dependently potentiates not only calcium-induced c-fos expression but also calcium-induced ERK activation. In the presence of PD98059, the amplification of calcium-induced c-fos expression by NO was not observed. This result suggests that calcium- and NO-signals converge into the MEK/ERK pathway, thereby enhance IEG expressions in neuronal cells.
authors.affiliation: Department of Physiology, College of Medicine, Dong-A University, South Korea.
authors.forename: S A
authors.initials: SA
authors.lastname: Lee
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.forename: E K
authors.initials: EK
authors.lastname: Kang
authors.forename: H R
authors.initials: HR
authors.lastname: Bae
authors.forename: K W
authors.initials: KW
authors.lastname: Bae
authors.forename: H T
authors.initials: HT
authors.lastname: Park
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D016716:PC12 Cells; D011189:Potassium Chloride / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D002147:Calmodulin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D011810:Quinoxalines; D013449:Sulfonamides; D009599:Nitroprusside; D009569:Nitric Oxide; C031938:calmidazolium; C002385:linsidomine; D011189:Potassium Chloride; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D008981:Molsidomine; D017871:Calcium-Calmodulin-Dependent 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; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium