title: Light-evoked S-nitrosylation in the retina.
abstract: Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pretreatment with N-ethylmaleimide (NEM), which occludes S-nitrosylation, or with 1-(2-trifluromethylphenyl)imidazole (TRIM), an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant posttranslational modification affecting a wide range of proteins under physiological conditions.
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Tooker
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Vigh
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D006054:Goldfish; D008027:Light; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010775:Photic Stimulation; D012160:Retina / Q000378:metabolism* / Q000528:radiation effects*; D026403:S-Nitrosothiols / Q000378:metabolism*; D013045:Species Specificity; D046509:Tissue Culture Techniques
chemical_list: D004791:Enzyme Inhibitors; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D003545:Cysteine; D005033:Ethylmaleimide
keywords: RRID; RRID: AB_881716; RRID: AB_2168539; RRID: AB_92588; RRID: AB_218559; RRID: IMSR_JAX:000664; RRID: IMSR_JAX:008519; RRID: OMICS_03354; RRID: nif- 0000-30467; RRID:nlx_53981; S-nitrosylation; goldfish; mouse; nitric oxide; retina; rid_000081
references.citation: J Microsc. 2006 Dec;224(Pt 3):213-32
references.pmid: 17210054
references.citation: Neuropharmacology. 1994 Nov;33(11):1235-44
references.pmid: 7870284
references.citation: J Biol Chem. 2007 May 11;282(19):13977-83
references.pmid: 17376775
references.citation: Nat Cell Biol. 2001 Feb;3(2):193-7
references.pmid: 11175752
references.citation: Am J Physiol. 1997 Dec;273(6 Pt 1):C1849-58
references.pmid: 9435489
references.citation: Rapid Commun Mass Spectrom. 2007;21(17):2797-804
references.pmid: 17661312
references.citation: Cell. 2001 Sep 21;106(6):675-83
references.pmid: 11572774
references.citation: Chem Biol. 1996 Aug;3(8):655-9
references.pmid: 8807899
references.citation: Vis Neurosci. 1997 Jul-Aug;14(4):717-29
references.pmid: 9279000
references.citation: J Neurosci. 2014 Jun 4;34(23):7845-61
references.pmid: 24899708
references.citation: Nature. 1997 Dec 18-25;390(6661):694-8
references.pmid: 9414163
references.citation: J Physiol. 2002 Jul 1;542(Pt 1):211-20
references.pmid: 12096062
references.citation: Neuron. 2013 May 22;78(4):596-614
references.pmid: 23719160
references.citation: Nat Rev Mol Cell Biol. 2005 Feb;6(2):150-66
references.pmid: 15688001
references.citation: Sci China C Life Sci. 1997 Feb;40(1):71-8
references.pmid: 18726301
references.citation: Chem Biol. 2008 Dec 22;15(12):1307-16
references.pmid: 19101475
references.citation: J Comp Neurol. 2010 Aug 1;518(15):3130-48
references.pmid: 20533364
references.citation: Nature. 1995 Oct 26;377(6551):734-7
references.pmid: 7477263
references.citation: Vis Neurosci. 2011 Mar;28(2):137-44
references.pmid: 21324227
references.citation: Methods. 2013 Aug 1;62(2):161-4
references.pmid: 23748109
references.citation: Exp Neurol. 2014 Nov;261:510-7
references.pmid: 25116452
references.citation: J Neurosci. 1994 Dec;14(12):7641-54
references.pmid: 7527846
references.citation: Neurosci Lett. 1988 Dec 5;94(3):247-52
references.pmid: 3205402
references.citation: Prog Retin Eye Res. 1998 Apr;17(2):207-30
references.pmid: 9695793
references.citation: J Neurosci. 2013 Dec 4;33(49):19176-93
references.pmid: 24305814
references.citation: J Neurophysiol. 1996 Oct;76(4):2307-15
references.pmid: 8899605
references.citation: Vis Neurosci. 2002 May-Jun;19(3):373-80
references.pmid: 12392185
references.citation: Vis Neurosci. 2013 May;30(3):91-103
references.pmid: 23721886
references.citation: J Comp Neurol. 1992 Jun 22;320(4):521-30
references.pmid: 1629402
references.citation: Brain Res. 2012 Jan 9;1430:112-25
references.pmid: 22133309
references.citation: Vis Neurosci. 1999 Jul-Aug;16(4):653-65
references.pmid: 10431914
references.citation: Microsc Res Tech. 2000 Sep 1;50(5):347-59
references.pmid: 10941171
references.citation: Brain Res. 1996 Dec 16;743(1-2):353-6
references.pmid: 9017268
references.citation: J Neurosci. 2002 May 15;22(10):3987-93
references.pmid: 12019318
references.citation: J Neurosci. 2004 Jul 21;24(29):6621-8
references.pmid: 15269274
references.citation: J Vis. 2007;7(14):7.1-13
references.pmid: 18217802
references.citation: Mol Vis. 2006;12:1543-51
references.pmid: 17200653
references.citation: Neuroreport. 2003 Oct 6;14(14):1763-6
references.pmid: 14534416
references.citation: J Neurophysiol. 2000 Jan;83(1):198-206
references.pmid: 10634867
references.citation: J Neurochem. 1999 Jun;72(6):2506-15
references.pmid: 10349861
references.citation: Vision Res. 2005 Dec;45(28):3469-86
references.pmid: 16171845
references.citation: J Physiol. 1997 Mar 15;499 ( Pt 3):689-99
references.pmid: 9130165
references.citation: J Biol Chem. 2012 Jan 20;287(4):2364-77
references.pmid: 22123824
references.citation: J Neurosci. 2012 Apr 4;32(14):4861-6
references.pmid: 22492042
references.citation: J Comp Neurol. 2010 Jul 1;518(13):2456-74
references.pmid: 20503422
references.citation: Vis Neurosci. 1990 Sep;5(3):223-30
references.pmid: 2134845
references.citation: J Comp Neurol. 2000 Aug 14;424(1):1-23
references.pmid: 10888735
references.citation: Trends Neurosci. 2002 Oct;25(10):510-7
references.pmid: 12220879
references.citation: Cardiovasc Res. 2010 Mar 1;85(4):796-805
references.pmid: 19914929
references.citation: J Neurosci. 2011 Nov 2;31(44):15884-93
references.pmid: 22049431
references.citation: J Biol Chem. 2008 Jul 4;283(27):18841-51
references.pmid: 18463095
references.citation: Vision Res. 1999 Jul;39(14):2299-303
references.pmid: 10367050
references.citation: Science. 2010 Jul 23;329(5990):413-7
references.pmid: 20576849
references.citation: J Physiol. 1989 Jul;414:351-75
references.pmid: 2558170
references.citation: J Comp Neurol. 1990 Nov 15;301(3):433-42
references.pmid: 2262600
references.citation: Endocrinology. 2002 Jul;143(7):2767-74
references.pmid: 12072412
references.citation: Nature. 1994 Apr 28;368(6474):850-3
references.pmid: 7512692
references.citation: J Comp Neurol. 2005 Mar 14;483(3):278-91
references.pmid: 15682393
references.citation: Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F628-40
references.pmid: 23804448
references.citation: Exp Eye Res. 2010 Nov;91(5):700-9
references.pmid: 20732319
references.citation: Curr Opin Chem Biol. 2011 Feb;15(1):129-36
references.pmid: 21087893
references.citation: Nat Neurosci. 2000 Jan;3(1):15-21
references.pmid: 10607390
references.citation: Neuron. 1997 May;18(5):691-6
references.pmid: 9182795
references.citation: Front Cell Neurosci. 2013 Oct 31;7:190
references.pmid: 24198758
references.citation: J Comp Neurol. 1998 Jun 22;396(1):131-40
references.pmid: 9623892
references.citation: Eur J Neurosci. 2005 Apr;21(8):2199-208
references.pmid: 15869516
references.citation: Mol Cell Proteomics. 2002 Apr;1(4):293-303
references.pmid: 12096111
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14330-5
references.pmid: 21844361
references.citation: J Neurophysiol. 2006 May;95(5):2866-77
references.pmid: 16467419
references.citation: Br J Pharmacol. 1996 Sep;119(2):423-31
references.pmid: 8886430
references.citation: Vision Res. 2009 May;49(9):943-59
references.pmid: 18722397
references.citation: Annu Rev Physiol. 1994;56:141-68
references.pmid: 8010738
references.citation: J Am Soc Mass Spectrom. 2008 Sep;19(9):1353-60
references.pmid: 18635375
references.citation: J Neurosci Res. 2007 May 15;85(7):1579-91
references.pmid: 17342779
references.citation: Cell. 1994 Sep 23;78(6):931-6
references.pmid: 7923362
references.citation: Anal Chem. 2003 Sep 1;75(17):4646-58
references.pmid: 14632076
references.citation: Biochem J. 1994 Mar 1;298 ( Pt 2):249-58
references.pmid: 7510950
references.citation: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4747-53
references.pmid: 16303975
references.citation: Vis Neurosci. 2009 May-Jun;26(3):275-86
references.pmid: 19602301
references.citation: Brain Res. 2007 Jul 2;1156:112-9
references.pmid: 17499222
references.citation: J Neurosci. 1999 Mar 1;19(5):1728-35
references.pmid: 10024359
references.citation: Invest Ophthalmol Vis Sci. 1995 Oct;36(11):2228-37
references.pmid: 7558716
references.citation: Neuron. 1994 Aug;13(2):315-24
references.pmid: 7520253
references.citation: Science. 2004 May 28;304(5675):1328-31
references.pmid: 15105460
references.citation: J Neurosci Res. 2009 Nov 1;87(14):3134-42
references.pmid: 19479987
references.citation: Invest Ophthalmol Vis Sci. 1998 Apr;39(5):850-3
references.pmid: 9538896
references.citation: J Neurosci. 1995 Jul;15(7 Pt 1):5004-13
references.pmid: 7623129
references.citation: Biochem J. 2008 Aug 1;413(3):479-91
references.pmid: 18452404