Open Access

Nitric oxide prevents phosphorylation of neuronal nitric oxide synthase at Serine1412 by inhibiting the Akt/PKB and CaM-K II signaling pathways

  • Authors:
    • Tao Song
    • Naoya Hatano
    • Katsuyoshi Sugimoto
    • Mariko Horii
    • Fuminori Yamaguchi
    • Masaaki Tokuda
    • Yoshiaki Miyamoto
    • Toshie Kambe
    • Yasuo Watanabe
  • View Affiliations

  • Published online on: April 20, 2012     https://doi.org/10.3892/ijmm.2012.971
  • Pages: 15-20
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Abstract

Neuronal nitric oxide synthase (nNOS) is an important regulatory enzyme in the central nervous system catalyzing the production of NO, which regulates multiple biological processes in the central nervous system. However, the mechanisms by which nNOS activity is regulated are not completely understood. In the present study, the effects of protein kinases on the phosphorylation of nNOS in GH3 rat pituitary tumor cells were evaluated. We show that phosphorylation of nNOS at Ser1412 could be induced by the phosphatidylinositol 3-kinase/protein kinase B (Akt/PKB) agonist insulin, the calcium/calmodulin-dependent protein kinase II (CaM-K II) agonist A23187 or the cAMP-dependent protein kinase A (PKA) agonist IBMX, respectively. The phosphorylation levels of nNOS at Ser1412, induced by activation of Akt/PKB or CaM-K II, but not by PKA signaling, were reduced by pre-treatment with the NO donor diethylamine-NONOate. This inhibitory effect could be reversed by addition of a reducing reagent, dithiothreitol. Furthermore, the levels of phosphorylation of nNOS at Ser1412, induced by Akt/PKB or CaM-K II but not by PKA signaling, were enhanced by inhibition of nNOS activity with 7-nitroindazole. These findings suggest that the activation of nNOS can be catalyzed by at least three protein kinases, Akt/PKB, CaM-K II or PKA. NO generated from nNOS feedback prevents the activation of nNOS by inhibiting either Akt/PKB or CaM-K II but not PKA signaling.

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July 2012
Volume 30 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Song T, Hatano N, Sugimoto K, Horii M, Yamaguchi F, Tokuda M, Miyamoto Y, Kambe T and Watanabe Y: Nitric oxide prevents phosphorylation of neuronal nitric oxide synthase at Serine1412 by inhibiting the Akt/PKB and CaM-K II signaling pathways. Int J Mol Med 30: 15-20, 2012
APA
Song, T., Hatano, N., Sugimoto, K., Horii, M., Yamaguchi, F., Tokuda, M. ... Watanabe, Y. (2012). Nitric oxide prevents phosphorylation of neuronal nitric oxide synthase at Serine1412 by inhibiting the Akt/PKB and CaM-K II signaling pathways. International Journal of Molecular Medicine, 30, 15-20. https://doi.org/10.3892/ijmm.2012.971
MLA
Song, T., Hatano, N., Sugimoto, K., Horii, M., Yamaguchi, F., Tokuda, M., Miyamoto, Y., Kambe, T., Watanabe, Y."Nitric oxide prevents phosphorylation of neuronal nitric oxide synthase at Serine1412 by inhibiting the Akt/PKB and CaM-K II signaling pathways". International Journal of Molecular Medicine 30.1 (2012): 15-20.
Chicago
Song, T., Hatano, N., Sugimoto, K., Horii, M., Yamaguchi, F., Tokuda, M., Miyamoto, Y., Kambe, T., Watanabe, Y."Nitric oxide prevents phosphorylation of neuronal nitric oxide synthase at Serine1412 by inhibiting the Akt/PKB and CaM-K II signaling pathways". International Journal of Molecular Medicine 30, no. 1 (2012): 15-20. https://doi.org/10.3892/ijmm.2012.971