title: Nitric oxide promotes nicotine-triggered ERK signaling via redox reactions in PC12 cells.
abstract: Nitric oxide (NO), produced by neuronal NO synthase (nNOS), serves as a signaling molecule with diverse biological responses in the central nervous system (CNS). In the present study, we demonstrated that nNOS expression enhances the nicotine-triggered activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in nNOS-transfected PC12 (NPC12) cells. Treatment with nicotine increased the phosphorylation level of ERK1/2 in the NPC12 cells as compared with that in control PC12 cells. However, nicotine treatment failed to enhance ERK1/2 phosphorylation when NPC12 cells were pretreated with several selective inhibitors of NOS, the nicotinic acetylcholine receptors, L-type voltage-dependent Ca(2+) channels, protein kinase C, Src, epidermal growth factor receptor, and MEK. The nicotine-induced ERK1/2 phosphorylation in PC12 cells was observed by their pretreatment with a NO donor. Moreover, the enhancement of nicotine-induced ERK1/2 phosphorylation in the NPC12 cells was regulated by intracellular glutathione levels, but not by the soluble guanylate cyclase-cGMP-protein kinase G signaling. Meanwhile, depolarization stimulated ERK1/2 phosphorylation in both PC12 and NPC12 cells. Taken together, these findings suggest that nicotine modulates NO-dependent redox condition; the resulting calcium influx, would increase ERK1/2 phosphorylation in nNOS expressing cells. Blockade of NO pathway may be selective target to reduce ERK1/2 phosphorylation via attenuation of the nicotine responses in the CNS.
authors: Laboratory of Pharmacology, High Technology Research Center, Showa Pharmaceutical University, Machida, Japan. miyamoto@pha.u-toyama.ac.jp
authors: Yoshiaki
authors: Y
authors: Miyamoto
authors: Ryosuke
authors: R
authors: Sakai
authors: Chiharu
authors: C
authors: Maeda
authors: Tsuyoshi
authors: T
authors: Takata
authors: Hideshi
authors: H
authors: Ihara
authors: Yukihiro
authors: Y
authors: Tsuchiya
authors: Yasuo
authors: Y
authors: Watanabe
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis / Q000378:metabolism; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D009538:Nicotine; D052248:Nitric Oxide Synthase Type I; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium