title: Nitric Oxide Synthase Activation as a Trigger of N-methyl-N-nitrosourea-Induced Photoreceptor Cell Death.
abstract: Retinal degeneration (RD) such as retinitis pigmentosa and age-related macular degeneration are major causes of blindness in adulthood. As one of the model for RD, intraperitoneal injection of N-methyl-N-nitrosourea (MNU) is widely used because of its selective photoreceptor cell death. It has been reported that MNU increases intracellular calcium ions in the retina and induces photoreceptor cell death. Although calcium ion influx triggers the neuronal nitric oxide synthase (nNOS) activation, the role of nNOS on photoreceptor cell death by MNU has not been reported yet. In this study, we investigated the contribution of nNOS on photoreceptor cell death induced by MNU in mice. MNU significantly increased NOS activation at 3 day after treatment. Then, we evaluated the effect of nNOS specific inhibitor, ethyl[4-(trifluoromethyl) phenyl]carbamimidothioate (ETPI) on the MNU-induced photoreceptor cell death. At 3 days, ETPI clearly inhibited the MNU-induced cell death in the ONL. These data indicate that nNOS is a key molecule for pathogenesis of MNU-induced photoreceptor cell death.
authors.affiliation: Department of Clinical Laboratory Science, Department of Molecular Neurobiology, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, 920-0942, Kanazawa, Japan. ef.ef.soylatte.ts@gmail.com.
authors.forename: Suguru
authors.initials: S
authors.lastname: Hisano
authors.affiliation: Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Sciences, 3500-3 Minamitamagaki, 513-8670, Suzuka, Japan. koriyama@suzuka-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Koriyama
authors.affiliation: Wellness Promotion Science Center, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, 920-0942, Kanazawa, Japan. kazuhiro@staff.kanazawa-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogai
authors.affiliation: Department of Clinical Laboratory Sciences, Graduate School of Medical Science, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, 920-0942, Kanazawa, Japan. sugitani@staff.kanazawa-u.ac.jp.
authors.forename: Kayo
authors.initials: K
authors.lastname: Sugitani
authors.affiliation: Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University, 13-1 Takaramachi, 920-8640, Kanazawa, Japan. satoru@med.kanazawa-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kato
mesh_terms: D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008297:Male; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D009252:NADPH Dehydrogenase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000201:enzymology; D055211:Retinal Photoreceptor Cell Inner Segment / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000477:Alkylating Agents; D004791:Enzyme Inhibitors; C000606304:ethyl (4-(trifluoromethyl)phenyl)carbamimidothioate; D008770:Methylnitrosourea; D052248:Nitric Oxide Synthase Type I; D009252:NADPH Dehydrogenase; D013890:Thiourea
keywords: N-methyl-N-mitrosourea; Neural nitric oxide synthease; Oxidative stress; Photoreceptor cell death