Nitric oxide enhances increase in cytosolic Ca2+ and promotes nicotine-triggered MAPK pathway in PC12 cells

Aya Kajiwara, Yukihiro Tsuchiya, Tsuyoshi Takata, Mayumi Nyunoya, Naohito Nozaki, Hideshi Ihara, Yasuo Watanabe

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The purpose of this study was to investigate the roles of neuronal nitric oxide synthase (nNOS), Ca2+/calmodulin (CaM)-dependent protein kinases (CaMKs), and protein kinase C (PKC) in nicotine-induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) activation. Treatment with nicotine stimulated ERK1/2 and p38 MAPK phosphorylation in the PC12 cells expressing nNOS (NPC12 cells) as compared with that in control PC12 cells. An inhibitor of L-type voltage- sensitive Ca2+ channel suppressed the nicotine-induced phosphorylation of p38 MAPK. The inhibition of CaMK-kinase, the upstream activator of CaMKI and CaMKIV, did not inhibit the enhanced their phosphorylation. ERK1/2 phosphorylation was attenuated by inhibitors of p38 MAPK, PKC, and MAPK-kinase 1/2, indicating the involvement of these protein kinases upstream of ERK1/2. Furthermore, we found that nNOS expression enhances the nicotine-induced increase in the intracellular concentration of Ca2+, using the Ca2+-sensitive fluorescent probe Fura2. These data suggest that NO promotes nicotine-triggered Ca2+ transient in PC12 cells to activate possibly CaMKII, leading to sequential phosphorylation of p38 MAPK and ERK1/2.

Original languageEnglish
Pages (from-to)3-9
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Volume34
DOIs
Publication statusPublished - 2013 Jan 1
Externally publishedYes

Keywords

  • Calmodulin-dependent protein kinase
  • ERK1/2
  • NO
  • P38 MAPK
  • PC12 cells

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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