title: 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.
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagane
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamori
authors.affiliation: Laboratory of Biochemistry, Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Niwa
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Electronic address: inanami@vetmed.hokudai.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D016227:Benzoquinones / Q000737:chemistry; D002417:Cattle; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D042783:Endothelial Cells / Q000166:cytology / Q000528:radiation effects*; D015971:Gene Expression Regulation, Enzymologic; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D047029:Lactams, Macrocyclic / Q000737:chemistry; D009025:Morpholines / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D011839:Radiation, Ionizing; D013892:Thioxanthenes / Q000737:chemistry; D013997:Time Factors; D014965:X-Rays
chemical_list: C546193:2-(2,6-dimethylmorpholin-4-yl)-N-(5-(6-morpholin-4-yl-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009025:Morpholines; D013892:Thioxanthenes; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D064007:Ataxia Telangiectasia Mutated Proteins; C001277:geldanamycin
keywords: ATM; DNA damage response; Endothelial nitric oxide synthase; HSP90; Ionizing radiation