Nitric oxide promotes nicotine-triggered ERK signaling via redox reactions in PC12 cells

Yoshiaki Miyamoto, Ryosuke Sakai, Chiharu Maeda, Tsuyoshi Takata, Hideshi Ihara, Yukihiro Tsuchiya, Yasuo Watanabe

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)344-349
Number of pages6
JournalNitric Oxide - Biology and Chemistry
Issue number3
Publication statusPublished - 2011 Oct 30
Externally publishedYes


  • ERK phosphorylation
  • NO
  • Nicotine
  • PC12 cells
  • Redox reactions

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research


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