Unbalanced redox status network as an early pathological event in congenital cataracts.
Cataracts
Glutathione
Proteomics
Redox status
Taurine
Ubiquitin
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
21
06
2023
revised:
08
08
2023
accepted:
31
08
2023
medline:
13
9
2023
pubmed:
8
9
2023
entrez:
7
9
2023
Statut:
ppublish
Résumé
The lens proteome undergoes dramatic composition changes during development and maturation. A defective developmental process leads to congenital cataracts that account for about 30% of cases of childhood blindness. Gene mutations are associated with approximately 50% of early-onset forms of lens opacity, with the remainder being of unknown etiology. To gain a better understanding of cataractogenesis, we utilized a transgenic mouse model expressing a mutant ubiquitin protein in the lens (K6W-Ub) that recapitulates most of the early pathological changes seen in human congenital cataracts. We performed mass spectrometry-based tandem-mass-tag quantitative proteomics in E15, P1, and P30 control or K6W-Ub lenses. Our analysis identified targets that are required for early normal differentiation steps and altered in cataractous lenses, particularly metabolic pathways involving glutathione and amino acids. Computational molecular phenotyping revealed that glutathione and taurine were spatially altered in the K6W-Ub cataractous lens. High-performance liquid chromatography revealed that both taurine and the ratio of reduced glutathione to oxidized glutathione, two indicators of redox status, were differentially compromised in lens biology. In sum, our research documents that dynamic proteome changes in a mouse model of congenital cataracts impact redox biology in lens. Our findings shed light on the molecular mechanisms associated with congenital cataracts and point out that unbalanced redox status due to reduced levels of taurine and glutathione, metabolites already linked to age-related cataract, could be a major underlying mechanism behind lens opacities that appear early in life.
Identifiants
pubmed: 37677999
pii: S2213-2317(23)00270-7
doi: 10.1016/j.redox.2023.102869
pmc: PMC10495660
pii:
doi:
Substances chimiques
Proteome
0
Glutathione
GAN16C9B8O
Mutant Proteins
0
Taurine
1EQV5MLY3D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
102869Subventions
Organisme : NEI NIH HHS
ID : R01 EY028559
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY015128
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY028927
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY014800
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Exp Eye Res. 2017 Mar;156:103-111
pubmed: 27373973
Neurobiol Aging. 2018 Nov;71:223-233
pubmed: 30172221
Mol Cell. 2011 Oct 21;44(2):325-40
pubmed: 21906983
Exp Eye Res. 2016 Sep;150:62-70
pubmed: 27142256
Neurochem Int. 2023 Sep;168:105554
pubmed: 37257587
Front Physiol. 2019 Jun 04;10:688
pubmed: 31231240
Cell Mol Biol Lett. 2021 Jan 5;26(1):1
pubmed: 33402098
Molecules. 2017 Nov 27;22(12):
pubmed: 29186888
Front Cell Neurosci. 2016 Apr 28;10:103
pubmed: 27199657
PLoS Biol. 2009 Mar;7(3):e1000074
pubmed: 19855814
Pathophysiology. 2006 Aug;13(3):151-62
pubmed: 16765571
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
J Cell Sci. 2016 Mar 1;129(5):875-80
pubmed: 26906419
Exp Eye Res. 2005 May;80(5):709-25
pubmed: 15862178
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Clin Exp Ophthalmol. 2020 Nov;48(8):1031-1042
pubmed: 32462803
Br J Nutr. 2010 Nov;104(10):1460-70
pubmed: 20691125
Exp Eye Res. 1984 Feb;38(2):177-9
pubmed: 6143681
J Biol Chem. 2004 Feb 6;279(6):3916-24
pubmed: 14638690
Hum Mol Genet. 2004 Apr 15;13(8):807-17
pubmed: 14976165
Invest Ophthalmol Vis Sci. 2014 Dec 23;56(1):598-605
pubmed: 25537203
Exp Eye Res. 1983 Oct;37(4):379-84
pubmed: 6641821
Biomed Res Int. 2015;2015:345219
pubmed: 26339607
Nat Protoc. 2011 Jun;6(6):743-60
pubmed: 21637195
Nucleic Acids Res. 2018 Jan 4;46(D1):D875-D885
pubmed: 29036527
Hum Mol Genet. 2019 Jan 1;28(1):96-104
pubmed: 30239721
Exp Eye Res. 1998 Nov;67(5):597-601
pubmed: 9878222
J Neurocytol. 2001 Jul;30(7):593-654
pubmed: 12118163
Graefes Arch Clin Exp Ophthalmol. 2009 Jan;247(1):115-20
pubmed: 18766362
Exp Eye Res. 2017 Jan;154:70-78
pubmed: 27838309
Exp Eye Res. 2016 May;146:318-329
pubmed: 26992777
Exp Eye Res. 2017 Mar;156:95-102
pubmed: 27334249
Neurochem Res. 1986 Apr;11(4):535-42
pubmed: 3724960
Adv Exp Med Biol. 2019;1185:365-370
pubmed: 31884639
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284
pubmed: 21890473
J Neurosci. 2002 Jan 15;22(2):413-27
pubmed: 11784786
FASEB J. 2016 Mar;30(3):1087-95
pubmed: 26590164
Exp Eye Res. 2016 Feb;143:68-74
pubmed: 26500196
Methods Mol Biol. 2006;328:159-75
pubmed: 16785648
Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):100-107
pubmed: 29332127
J Neurosci. 1995 Jul;15(7 Pt 2):5106-29
pubmed: 7623139
Science. 2023 Jun 9;380(6649):eabn9257
pubmed: 37289866
PLoS One. 2010 Oct 20;5(10):e13331
pubmed: 20975996
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
FASEB J. 1995 Sep;9(12):1173-82
pubmed: 7672510
Antioxidants (Basel). 2022 Oct 01;11(10):
pubmed: 36290696
J Biol Chem. 2005 May 27;280(21):20365-74
pubmed: 15790562
Trends Endocrinol Metab. 2020 Apr;31(4):320-329
pubmed: 32187524
PLoS One. 2017 Apr 18;12(4):e0175491
pubmed: 28419112
FEBS Lett. 2002 Nov 6;531(2):162-7
pubmed: 12417305
EMBO J. 2014 Nov 3;33(21):2473-91
pubmed: 25216678
Free Radic Biol Med. 2017 Dec;113:84-96
pubmed: 28951044
J Proteome Res. 2014 Mar 7;13(3):1177-89
pubmed: 24450463
Eur Rev Med Pharmacol Sci. 2021 Jul;25(13):4520-4526
pubmed: 34286494
Amino Acids. 2002;23(1-3):337-42
pubmed: 12373556
Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1071-6
pubmed: 25583491
FASEB J. 2002 Feb;16(2):231-3
pubmed: 11772953
Ophthalmic Genet. 2011 Jun;32(2):75-9
pubmed: 21268678
Exp Eye Res. 2014 Aug;125:71-8
pubmed: 24910091
Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1978 Jan 31;205(2):73-9
pubmed: 305215
Int J Dev Biol. 2008;52(7):873-86
pubmed: 18956317
J Nutr. 1948 Aug;36(2):277-95
pubmed: 18876490
Antioxidants (Basel). 2021 Nov 24;10(12):
pubmed: 34942978
Biochem J. 2006 Feb 15;394(Pt 1):267-73
pubmed: 16262602
Curr Eye Res. 2017 Mar;42(3):402-410
pubmed: 27348130
Proc Soc Exp Biol Med. 1972 Jul;140(3):1103-7
pubmed: 5064698
Neurotox Res. 2016 Jul;30(1):67-75
pubmed: 26966009
Nat Cell Biol. 2015 Feb;17(2):160-9
pubmed: 25621951
Anal Chem. 2003 Apr 15;75(8):1895-904
pubmed: 12713048
Anal Biochem. 1980 Jul 15;106(1):55-62
pubmed: 7416469
Cell. 2023 Jan 19;186(2):346-362.e17
pubmed: 36638793
Hum Genome Var. 2017 Jun 08;4:17019
pubmed: 28611923
Biochim Biophys Acta Mol Cell Res. 2023 Apr;1870(4):119450
pubmed: 36871745
Biochim Biophys Acta. 2016 Aug;1862(8):1433-42
pubmed: 27155571
J Ocul Pharmacol Ther. 2000 Apr;16(2):121-35
pubmed: 10803423
Proc Natl Acad Sci U S A. 2015 May 26;112(21):6637-42
pubmed: 25969509
J Neurosci Res. 2009 Jan;87(1):208-17
pubmed: 18683245
Curr Eye Res. 2023 Jan;48(1):25-33
pubmed: 36300537