title: Nitric oxide (NO.) stabilizes whereas nitrosonium (NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro.
abstract: Recent observations suggest that nitric oxide (NO(.)) can increase or decrease growth cone motility. Here, these apparently paradoxical results are explained by distinct actions of different NO-related species. Filopodial morphology of 223 rat retinal ganglion cells was monitored under computer-enhanced video microscopy in the presence of NO synthase (NOS) substrates or inhibitors, donors of specific NO-related species, and membrane-permeant cyclic nucleotide analogs. Physiological NOS activity induced filopodial outgrowth, whereas inhibition of NOS stabilized filopodia. Similar to NOS, nitrosonium (NO(+) transfer) and peroxynitrite (ONOO(-)), which can regulate the activity of growth-associated proteins by S-nitrosylation and oxidation, respectively, induced filopodial outgrowth. In contrast, NO(.), which stimulates guanylate cyclase to increase cGMP, stabilized filopodial activity. Thus disparate NO-related species may offer a dynamic process of filopodial growth regulation.
authors.affiliation: Cerebrovascular and NeuroScience Research Institute, Brigham and Women's Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Cheung
authors.forename: I
authors.initials: I
authors.lastname: Bhan
authors.forename: S A
authors.initials: SA
authors.lastname: Lipton
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000648:ultrastructure; D026403:S-Nitrosothiols
chemical_list: D000975:Antioxidants; D020030:Nitric Oxide Donors; D009573:Nitrites; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; C039900:nitroxyl; D006152:Cyclic GMP; D003545:Cysteine