Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

• Nagane, Masaki

• Yasui, Hironobu

• Sakai, Yuri

• Yamamori, Tohru

• Niwa, Koichi

• Hattori, Yuichi

• Kondo, Takashi

• Inanami, Osamu

Abstract

In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

Journal

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 456 (1), 541-546, 2015-02

  Elsevier

Keywords

• Ionizing radiation
• endothelial nitric oxide synthase
• ATM
• HSP90
• DNA damage response

Details

• CRID: 1050001202676474752
• NII Article ID: 120005906762
• NII Book ID: AA00564395
• HANDLE: 2115/57811
• ISSN: 0006291X
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles