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

作者：Nagane Masaki; Yasui Hironobu; Sakai Yuri; Yamamori Tohru; Niwa Koichi; Hattori Yuichi; Kondo Takashi; Inanami Osamu^*

来源：Biochemical and Biophysical Research Communications, 2015, 456(1): 541-546.

DOI：10.1016/j.bbrc.2014.12.002

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

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.

• 出版日期2015-1-2