title: Nipradilol promotes axon regeneration through S-nitrosylation of PTEN in retinal ganglion cells.
abstract: Nipradilol (Nip) is registered as an anti-glaucoma agent. More recently, a protective effect of Nip has been demonstrated in retinal ganglion cells (RGCs) mediated by S-nitrosylation of antioxidative-related Keap1 protein due to its nitric oxide (NO)-donating effect. It also has been reported that Nip promoted axon outgrowth in cat RGCs. However, the detailed mechanism remains unclear. NO physiologically regulates numerous cellular responses through S-nitrosylation of protein at cysteine residues. It has been reported that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) deletion strongly showed axon regeneration after optic nerve injury. PTEN inactivation by S-nitrosylation results in the accumulation of phosphatidylinositol (3, 4, 5) triphosphate (PIP3) and the activation of Akt/mammalian target of rapamycin (mTOR) signaling. The ribosomal S6 kinase 1 (S6K) which can monitor as phospho-S6 (pS6) is one of major target of mTOR. In this study, we investigated the possibility that Nip can promote axon outgrowth in RGCs by Akt/mTOR signaling thorough S-nitrosylation of PTEN.
authors.affiliation: Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University, 13-1 Takaramachi, 920-8640, Kanazawa, Japan, koriyama@med.kanazawa-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Koriyama
authors.forename: Marie
authors.initials: M
authors.lastname: Kamiya
authors.forename: Kunizo
authors.initials: K
authors.lastname: Arai
authors.forename: Kayo
authors.initials: K
authors.lastname: Sugitani
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogai
authors.forename: Satoru
authors.initials: S
authors.lastname: Kato
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002461:Cell Line, Transformed; D005901:Glaucoma / Q000188:drug therapy*; D051379:Mice; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D009569:Nitric Oxide; C546843:mTOR protein, mouse; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C036089:nipradilol