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

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.
AuthorsMasaki Nagane, Hironobu Yasui, Yuri Sakai, Tohru Yamamori, Koichi Niwa, Yuichi Hattori, Takashi Kondo, Osamu Inanami
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 456 Issue 1 Pg. 541-6 (Jan 02 2015) ISSN: 1090-2104 [Electronic] United States
PMID25498542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • 2-(2,6-dimethylmorpholin-4-yl)-N-(5-(6-morpholin-4-yl-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide
  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Morpholines
  • Thioxanthenes
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Ataxia Telangiectasia Mutated Proteins
  • geldanamycin
Topics
  • Animals
  • Aorta (cytology, radiation effects)
  • Ataxia Telangiectasia Mutated Proteins (metabolism)
  • Benzoquinones (chemistry)
  • Cattle
  • Cytoplasm (metabolism)
  • DNA Damage
  • DNA Repair
  • Endothelial Cells (cytology, radiation effects)
  • Gene Expression Regulation, Enzymologic
  • HSP90 Heat-Shock Proteins (metabolism)
  • Immunohistochemistry
  • Lactams, Macrocyclic (chemistry)
  • Morpholines (chemistry)
  • Nitric Oxide Synthase (metabolism)
  • Nitric Oxide Synthase Type III (metabolism)
  • Phosphorylation
  • Radiation, Ionizing
  • Thioxanthenes (chemistry)
  • Time Factors
  • X-Rays

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