title: L-arginine promotes DNA repair in cultured bronchial epithelial cells exposed to ozone: involvement of the ATM pathway.
abstract: Ozone may lead to DNA breaks in airway epithelial cells. p-ATM (phosphorylated ataxia telangiectasia mutated) plays a pivotal role in DNA repair. Derivatives of NO (nitric oxide) are regulators of the phosphorylation, and NO is increased under oxidative stress. The present study was aimed to study the effect of NO donor L-arg (L-arginine) on DNA damage repair in human bronchial epithelial cells exposed to ozone and the potential mechanisms involved. HBECs (human bronchial epithelial cells) were cultured with or without ozone (1.5 ppm, 30 min), DNA breaks were measured with a comet assay and agarose gel electrophoresis, cell cycling was determined by flow cytometry and p-ATM was measured by immunofluorescence and Western blot. Data were analysed by ANOVA (analysis of variance). P<0.05 was considered as significant. Ozone induced marked DNA breaks, G1-phase arrest and increased expression of p-ATM in HBECs, while wortmannin reduced the levels of p-ATM induced by ozone; the NO donor, L-arg, minimized the effects of ozone-induced DNA breaks and increased the level of p-ATM, while the NO synthase inhibitor, L-NMMA [N(G)-minomethyl-L-arginine], restrained those effects of L-arg. The effect of L-arg on DNA repair is NO-mediated, and p-ATM is implicated in the processes of DNA repair.
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Cui
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Gao
authors.forename: Guoying
authors.initials: G
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Fei
authors.initials: F
authors.lastname: Qu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tang
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Chaxiang
authors.initials: C
authors.lastname: Guan
mesh_terms: D001120:Arginine / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D001980:Bronchi / Q000166:cytology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D010126:Ozone; D001120:Arginine; D019001:Nitric Oxide Synthase; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases