Endogenous Nitric Oxide Generation Linked to Ryanodine Receptors Activates Cyclic GMP / Protein Kinase G Pathway for Cell Proliferation of Neural Stem/Progenitor Cells Derived From Embryonic Hippocampus

• Yoneyama Masanori

  Department of Pharmacology, Setsunan University Faculty of Pharmaceutical Sciences, Japan

• Kawada Koichi

  Department of Pharmacology, Setsunan University Faculty of Pharmaceutical Sciences, Japan

• Shiba Tatsuo

  Department of Pharmacology, Setsunan University Faculty of Pharmaceutical Sciences, Japan

• Ogita Kiyokazu

  Department of Pharmacology, Setsunan University Faculty of Pharmaceutical Sciences, Japan

Bibliographic Information

Other Title

• Endogenous nitric oxide generation linked to ryanodine receptors activates cyclic GMP/protein kinase G pathway for cell proliferation of neural stem/progenitor cells derived from embryonic hippocamp

Abstract

Nitric oxide (NO) activates the cyclic GMP (cGMP) / protein kinase G (PKG) pathway during physiological processes in numerous types of cells. Here, we evaluated whether this NO/cGMP/PKG pathway is involved in the proliferation of neural stem/progenitor cells (NPCs) derived from the hippocampus of embryonic mice. In culture, the exposure to the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME) significantly decreased the number of viable cells and 5-bromo-2′-deoxyuridine (BrdU) incorporation into the cells, as well as the levels of intracellular reactive oxygen species, extracellular NO₂, and intracellular cGMP. Like L-NAME, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and PKG inhibitor KT5823 also decreased cell viability and BrdU incorporation. The membrane-permeable cGMP analogue 8-bromo-cGMP partially abolished the L-NAME–induced decrease in the BrdU incorporation. BrdU incorporation was decreased by Ca²⁺-channel blockers, including dantrolene, MK-801, ifenprodil, and nifedipine. Interestingly, the NO₂ level was decreased by dantrolene, but not by the other 3 blockers. L-NAME and ODQ attenuated phosphorylation of Akt, but not that of extracellular signal-regulated kinases or epidermal growth factor receptors. Our data suggest that endogenous NO generation linked to dantrolene-sensitive ryanodine receptors activates the cGMP/PKG signaling pathway for positive regulation of proliferation of hippocampal NPCs derived from embryonic mice.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 115 (2), 182-195, 2011

  The Japanese Pharmacological Society

Keywords

• cyclic GMP / protein kinase G pathway
• neural stem/progenitor cells
• nitric oxide
• proliferation
• ryanodine receptor channel

Details

• CRID: 1390282680158061952
• NII Article ID: 10029892057
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.10290fp
• COI: 1:CAS:528:DC%2BC3MXivVKrtLk%3D
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 10979797
• PubMed: 21263206
• Web Site: http://id.ndl.go.jp/bib/10979797
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10979797
• Web Site: https://search.jamas.or.jp/link/ui/2012000089
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed