Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II

Tao Song, Naoya Hatano, Toshie Kambe, Yoshiaki Miyamoto, Hideshi Ihara, Hideyuki Yamamoto, Katsuyoshi Sugimoto, Kodai Kume, Fuminori Yamaguchi, Masaaki Tokuda, Yasuo Watanabe

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The mechanisms of NO inhibition of CaMK [Ca2+/CaM (calmodulin)-dependent protein kinase] II activity were studied. In rat pituitary tumour GH3 cells, TRH [thyrotrophin (TSH)-releasing hormone]-stimulated phosphorylation of nNOS [neuronal NOS (NO synthase)] at Ser847 was sensitive to an inhibitor of CaMKs, KN-93, and was enhanced by inhibition of nNOS with 7NI (7-nitroindazole). Enzyme activity of CaMKII following in situ treatment with 7NI was also increased. The in vitro activity of CaMKII was inhibited by co-incubation either with nNOS and L-arginine or with NO donors SNAP (S-nitroso-N-acetyl-DL-penicillamine) and DEA-NONOate [diethylamine-NONOate (diazeniumdiolate)]. Once inhibited by these treatments, CaMKII was observed to undergo full reactivation on the addition of a reducing reagent, DTT (dithiothreitol). In transfected cells expressing CaMKII and nNOS, treatment with the calcium ionophore A23187 further revealed nNOS phosphorylation at Ser847, which was enhanced by 7NI and CaMKII S-nitrosylation. Mutated CaMKII (C6A), in which Cys6 was substituted with an alanine residue, was refractory to 7NI-induced enhancement of nNOS phosphorylation or to CaMKII S-nitrosylation. Furthermore, we could identify Cys6 as a direct target for S-nitrosylation of CaMKII using MS. In addition, treatment with glutamate caused an increase in CaMKII S-nitrosylation in rat hippocampal slices. This glutamate-induced S-nitrosylation was blocked by 7NI. These results suggest that inactivation of CaMKII mediated by S-nitrosylation at Cys6 may contribute to NO-induced neurotoxicity in the brain.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalBiochemical Journal
Volume412
Issue number2
DOIs
Publication statusPublished - Jun 1 2008
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Nitric Oxide
Modulation
Phosphorylation
Rats
Glutamic Acid
Thyrotrophs
Penicillamine
Calcium Ionophores
Dithiothreitol
Calcimycin
Enzyme activity
Pituitary Neoplasms
Thyrotropin
Nitric Oxide Synthase
Alanine
Refractory materials
Arginine
Tumors

Keywords

  • Ca/calmodulin (CaM)-dependent protein kinase II (CaMKII)
  • Neuronal NO synthase (nNOS)
  • Phosphorylation
  • Pituitary tumour GH3 cells
  • Redox regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Song, T., Hatano, N., Kambe, T., Miyamoto, Y., Ihara, H., Yamamoto, H., ... Watanabe, Y. (2008). Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II. Biochemical Journal, 412(2), 223-231. https://doi.org/10.1042/BJ20071195

Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II. / Song, Tao; Hatano, Naoya; Kambe, Toshie; Miyamoto, Yoshiaki; Ihara, Hideshi; Yamamoto, Hideyuki; Sugimoto, Katsuyoshi; Kume, Kodai; Yamaguchi, Fuminori; Tokuda, Masaaki; Watanabe, Yasuo.

In: Biochemical Journal, Vol. 412, No. 2, 01.06.2008, p. 223-231.

Research output: Contribution to journalArticle

Song, T, Hatano, N, Kambe, T, Miyamoto, Y, Ihara, H, Yamamoto, H, Sugimoto, K, Kume, K, Yamaguchi, F, Tokuda, M & Watanabe, Y 2008, 'Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II', Biochemical Journal, vol. 412, no. 2, pp. 223-231. https://doi.org/10.1042/BJ20071195
Song, Tao ; Hatano, Naoya ; Kambe, Toshie ; Miyamoto, Yoshiaki ; Ihara, Hideshi ; Yamamoto, Hideyuki ; Sugimoto, Katsuyoshi ; Kume, Kodai ; Yamaguchi, Fuminori ; Tokuda, Masaaki ; Watanabe, Yasuo. / Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II. In: Biochemical Journal. 2008 ; Vol. 412, No. 2. pp. 223-231.
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AU - Yamamoto, Hideyuki

AU - Sugimoto, Katsuyoshi

AU - Kume, Kodai

AU - Yamaguchi, Fuminori

AU - Tokuda, Masaaki

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