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.
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Authors | Masaki Nagane, Hironobu Yasui, Yuri Sakai, Tohru Yamamori, Koichi Niwa, Yuichi Hattori, Takashi Kondo, Osamu Inanami |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 456
Issue 1
Pg. 541-6
(Jan 02 2015)
ISSN: 1090-2104 [Electronic] United States |
PMID | 25498542
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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