{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:14:12Z","timestamp":1792271652193,"version":"4.4.0"},"reference-count":119,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alcon Laboratories and the National Institute of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The ocular lens has a very high content of the antioxidant glutathione (GSH) and the enzymes that can recycle its oxidized form, glutathione disulfide (GSSG), for further use. It can be synthesized in the lens and, in part, transported from the neighboring anterior aqueous humor and posterior vitreous body. GSH is known to protect the thiols of the structural lens crystallin proteins from oxidation by reactive oxygen species (ROS) so the lens can maintain its transparency for proper visual function. Age-related lens opacity or senile cataract is the major visual impairment in the general population, and its cause is closely associated with aging and a constant exposure to environmental oxidative stress, such as ultraviolet light and the metabolic end product, H2O2. The mechanism for senile cataractogenesis has been hypothesized as the results of oxidation-induced protein-thiol mixed disulfide formation, such as protein-S-S-glutathione and protein-S-S-cysteine mixed disulfides, which if not reduced in time, can change the protein conformation to allow cascading modifications of various kinds leading to protein\u2013protein aggregation and insolubilization. The consequence of such changes in lens structural proteins is lens opacity. Besides GSH, the lens has several antioxidation defense enzymes that can repair oxidation damage. One of the specific redox regulating enzymes that has been recently identified is thioltransferase (glutaredoxin 1), which works in concert with GSH, to reduce the oxidative stress as well as to regulate thiol\/disulfide redox balance by preventing protein-thiol mixed disulfide accumulation in the lens. This oxidation-resistant and inducible enzyme has multiple physiological functions. In addition to protecting structural proteins and metabolic enzymes, it is able to regulate the redox signaling of the cells during growth factor-stimulated cell proliferation and other cellular functions. This review article focuses on describing the redox regulating functions of GSH and the thioltransferase enzyme in the ocular lens.<\/jats:p>","DOI":"10.3390\/antiox11101973","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T22:47:27Z","timestamp":1665182847000},"page":"1973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Glutathione and Glutaredoxin in Redox Regulation and Cell Signaling of the Lens"],"prefix":"10.3390","volume":"11","author":[{"given":"Marjorie F.","family":"Lou","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Department of Ophthalmology, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Department of Pharmaceutical Sciences, System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Berman, E.R. (1991). Biochemistry of the Eye, Plenum Press.","DOI":"10.1007\/978-1-4757-9441-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1001\/archopht.1964.00970020554022","article-title":"Selected topics in ophthalmic biochemistry","volume":"72","author":"Kinoshita","year":"1964","journal-title":"Arch. Ophthalmol."},{"key":"ref_3","unstructured":"Tasman, W., and Jaeger, E. (1991). Pathogenesis of cataracts. Clinical Ophthalmology, Lippincott Press."},{"key":"ref_4","unstructured":"Duncan, G. (1981). Protein modification in cataract: Possible oxidative mechanisms. Mechanisms of Cataract Formation in the Human Lens, Academic Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1096\/fasebj.9.12.7672510","article-title":"Oxidative stress-induced cataract: Mechanism of action","volume":"9","author":"Spector","year":"1995","journal-title":"FASEB J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0968-0004(81)90050-5","article-title":"Aging of protein molecules: Lens crystallins as a model system","volume":"6","author":"Zigler","year":"1981","journal-title":"Trends Biochem. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000055612","article-title":"Age-related nuclear cataract: A lens transport problem","volume":"32","author":"Truscott","year":"2000","journal-title":"Ophthalmic Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S1350-9462(03)00050-8","article-title":"Redox Regulation in the Lens","volume":"Volume 22","author":"Osborne","year":"2003","journal-title":"Progress in Retina and Eye Research"},{"key":"ref_9","first-page":"325","article-title":"Association of oxidative stress with cataractogenesis","volume":"Volume 15","author":"Fuchs","year":"2004","journal-title":"Redox-Genome Interactions in Health and Disease"},{"key":"ref_10","first-page":"802","article-title":"Ultraviolet radiation and the eye: An epidemiologic study","volume":"87","author":"Taylor","year":"1989","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3109\/02713688408997190","article-title":"Lenticular glutathione synthesis: Rate-limiting factors in its regulation and decline","volume":"3","author":"Rathbun","year":"1984","journal-title":"Curr. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/0014-4835(90)90127-G","article-title":"Glutathione and its function in the lens\u2014An Overview","volume":"50","author":"Reddy","year":"1990","journal-title":"Exp. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/jop.2000.16.121","article-title":"Glutathione: A vital lens antioxidant","volume":"16","author":"Giblin","year":"2000","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.exer.2006.01.028","article-title":"Molecular identification and characterization of the glycine transporter (GLYT1) and the glutamine\/glutamate transporter (ASCT2) in the rat lens","volume":"83","author":"Lim","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.exer.2013.09.002","article-title":"Molecular identification and cellular localization of a potential transport system involved in cysteine\/cysteine uptake in human lenses","volume":"116","author":"Lim","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1006\/exer.1994.1134","article-title":"Blood-to lens transport of reduced glutathione in an in situ perfused guinea pig eye","volume":"59","author":"Zlokovc","year":"1994","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.exer.2009.11.006","article-title":"Dynamic regulation of GSH synthesis and uptake pathways in the rat lens epithelium","volume":"90","author":"Li","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1167\/iovs.16-19592","article-title":"Evidence of dual mechanisms of glutathione uptake in the rodent lens: A novel role for vitreous humor in lens glutathione homeostasis","volume":"57","author":"Whitson","year":"2016","journal-title":"Investig. Ophthalmol. Vis Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/0014-4835(90)90133-F","article-title":"The Role of Protein-thiol Mixed Disulfides in Cataractogenesis","volume":"50","author":"Lou","year":"1990","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/0014-4835(86)90050-3","article-title":"Quantitation of Protein Mixed Disulfides by Ion-Exchange Chromatography","volume":"42","author":"Lou","year":"1986","journal-title":"Exp. Eye Res."},{"key":"ref_21","first-page":"883","article-title":"Normal and Cataractous Human Lenses: Re-evaluation of the Thiol\/disulfide and Protein Status","volume":"8","author":"Lou","year":"1989","journal-title":"Curr. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/0014-4835(92)90015-K","article-title":"Protein-thiol Mixed Disulfides in Human Lens","volume":"55","author":"Lou","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0304-4165(93)90057-F","article-title":"A New Mixed Disulfide Species in Human Cataractous and Aged Lenses","volume":"1157","author":"Dickerson","year":"1993","journal-title":"Biochem. Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1006\/exer.1993.1111","article-title":"The Effect and Recovery of Long Term H2O2 Exposure on Rat Lens Morphology and Biochemistry","volume":"57","author":"Cui","year":"1993","journal-title":"Exp. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1006\/exer.1996.0251","article-title":"Relationship of protein-GSH and thioltransferase in H2O2-induced cataract in cultured pig lens","volume":"64","author":"Wang","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1074\/jbc.274.8.4735","article-title":"Modification of \u03b3B-crystallins from a hydrogen peroxide treated bovine lens","volume":"274","author":"Hanson","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1006\/exer.1998.0638","article-title":"Correlation of protein-thiol mixed disulfide level with the opacity and brunescence in human lens","volume":"68","author":"Lou","year":"1999","journal-title":"Exp. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1006\/exer.1996.0149","article-title":"Increase in the intramolecular disulfide bonding of alpha-crystallin during aging of the human lens","volume":"63","author":"Takemoto","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"951","DOI":"10.3109\/02713689508995135","article-title":"Further Studies on the Dynamic Changes of Glutathione and Protein-thiol Mixed Disulfides in H2O2 Induced Cataract in Rat Lenses: Distributions and effect of aging","volume":"14","author":"Lou","year":"1995","journal-title":"Curr. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1042\/bj1170957","article-title":"Free and protein bound glutathione in normal and cataractous human lenses","volume":"117","author":"Harding","year":"1970","journal-title":"Biochem. J."},{"key":"ref_31","first-page":"153","article-title":"Protein-bound glutathione in mammalian lenses and in galactose cataract","volume":"8","author":"Reddy","year":"1976","journal-title":"Doc. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0014-4835(77)90126-9","article-title":"The state of sulphydryl groups in normal and cataractous human lenses","volume":"25","author":"Truscott","year":"1977","journal-title":"Exp. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1073\/pnas.75.7.3244","article-title":"Disulfide-linked high molecular weight protein associated with human cataract","volume":"75","author":"Spector","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Green, K., Edelhauser, H.F., Hackett, R.B., Hull, D.S., Potter, D.E., and Tripathi, R.C. (1997). Protein-thiol mixed disulfides and thioltransferase in the lens- a review. Advances in Ocular Toxicology, Plenum Press.","DOI":"10.1007\/978-1-4615-5937-5"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1089\/jop.2000.16.137","article-title":"Thiol regulation in the lens","volume":"16","author":"Lou","year":"2000","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1073\/pnas.73.7.2275","article-title":"Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione","volume":"73","author":"Holmgren","year":"1976","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1021\/bi00608a006","article-title":"Purification and characterization of cytoplasmic thioltransferase (glutathione: Disulfide oxidoreductase) from rat liver","volume":"17","author":"Axelsson","year":"1978","journal-title":"Biochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1016\/S0021-9258(18)48298-1","article-title":"The primary structure of pig liver thioltransferase","volume":"262","author":"Gan","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1432-1033.1995.tb20356.x","article-title":"Purification from placenta, amino acid sequence, structure comparisons and cDNA cloning of human Grx (thioltransferase)","volume":"227","author":"Padilla","year":"1995","journal-title":"Eur. J. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1093\/oxfordjournals.jbchem.a123819","article-title":"Study of human erythrocyte thioltransferase: Comparative characterization with bovine enzyme and its physiological role under oxidative stress","volume":"111","author":"Terada","year":"1992","journal-title":"J. Biochem."},{"key":"ref_41","unstructured":"Packer, L., and Cadenas, E.P. (1995). Glutathionyl specificity of thioltransferase: Mechanistic and physiological implications. Biothiols in Health and Disease, Marcel Dekker Inc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1089\/ars.2012.4644","article-title":"Protein-thiol oxidation and cell death: Regulatory role of glutaredoxins","volume":"17","author":"Allen","year":"2012","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1006\/exer.1996.0133","article-title":"Evidences for the Presence of Thioltransferase in the Lens","volume":"63","author":"Raghavachari","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_44","first-page":"743","article-title":"Recombinant human lens thioltransferase: Purification, characterization and function","volume":"42","author":"Qiao","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0014-5793(95)01066-N","article-title":"Cloning, expression and characterization of human thioltransferase (glutaredoxin) in E. coli","volume":"374","author":"Chrestensen","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0014-5793(95)01413-6","article-title":"High-level expression of fully active human glutaredoxin (thioltransferase) in E. coli and characterization of Cys 7 to Ser mutant protein","volume":"378","author":"Padilla","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0378-1119(97)00262-X","article-title":"The human glutaredoxin gene: Determination of its organization, transcription start point, and promoter analysis","volume":"197","author":"Park","year":"1997","journal-title":"Gene"},{"key":"ref_48","first-page":"476","article-title":"Distribution of thioltransferase in ocular tissues","volume":"39","author":"Wu","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1167\/iovs.05-0237","article-title":"Induction of thioltransferase and thiolredoxin\/thioredoxin reductase systems in cultured porcine lenses under oxidative stress","volume":"46","author":"Moon","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1167\/iovs.02-1322","article-title":"Cloning, expression and characterization of human lens thioredoxin","volume":"44","author":"Yegorova","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","first-page":"149","article-title":"Thioltransferases","volume":"66","author":"Wells","year":"1993","journal-title":"Adv. Enzymol. Relat. Areas Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.coph.2007.06.003","article-title":"Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stress","volume":"7","author":"Gallogly","year":"2007","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.bbagen.2008.06.003","article-title":"Glutaredoxin systems","volume":"1780","author":"Lillig","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10197","DOI":"10.1016\/j.redox.2021.101975","article-title":"Glutaredoxin: Discovery, redox defense and much more","volume":"43","author":"Ogata","year":"2021","journal-title":"Redox Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1006\/exer.2001.1103","article-title":"Effect of H2O2 on human lens epithelial cells and the possible mechanism for oxidative damage repair by thioltransferase","volume":"74","author":"Xing","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1006\/exer.1997.0464","article-title":"Thioltransferase is present in the lens epithelial cells as a highly oxidative stress-resistant enzyme","volume":"66","author":"Lou","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_57","first-page":"1002","article-title":"Regulation of thioltransferase expression in human lens epithelial cells","volume":"42","author":"Raghavachari","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12086","DOI":"10.1016\/S0021-9258(18)33682-2","article-title":"Biological disulfides: The third messenger? Modulation of phosphofructokinase activity by thiol\/disulfide exchange","volume":"257","author":"Gilbert","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1146\/annurev.bi.54.070185.001513","article-title":"Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation","volume":"54","author":"Ziegler","year":"1985","journal-title":"Annu. Rev. Biochem."},{"key":"ref_60","first-page":"239","article-title":"Effect of thioltransferase on the cystamine-activated fructose 1,6-biphosphatase by its redox regulation","volume":"32","author":"Terada","year":"1994","journal-title":"Biochem. Mol. Biol. Intl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1006\/exer.2000.0836","article-title":"Modulation of lens glycolytic pathway by thioltransferase","volume":"70","author":"Qiao","year":"2000","journal-title":"Exp. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/oxfordjournals.jbchem.a124500","article-title":"Possible differences in the regenerative roles played by thioltransferase and thioredoxin for oxidatively damaged proteins","volume":"116","author":"Yoshitake","year":"1994","journal-title":"J. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0014-4835(81)80052-8","article-title":"Stimulation of the hexose monophosphate shunt in rabbit lens in response to the oxidation of glutathione","volume":"33","author":"Giblin","year":"1981","journal-title":"Exp. Eye Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"15361","DOI":"10.1016\/S0021-9258(18)55401-6","article-title":"Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity","volume":"265","author":"Wells","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1167\/iovs.03-0545","article-title":"Thioltransferase mediated ascorbate recycling in human lens epithelial cells","volume":"45","author":"Fernando","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7276","DOI":"10.1167\/iovs.12-10482","article-title":"Ultraviolet radiation-induced cataract in mice: The effect of age and the potential biochemical mechanism","volume":"53","author":"Zhang","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","first-page":"1876","article-title":"Regulation of Human thioltransferase (hTTase) gene by AP-1 transcription factor under oxidative stress","volume":"43","author":"Krysan","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0955-0674(97)80068-3","article-title":"AP-1 function and regulation","volume":"9","author":"Karin","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1073\/pnas.94.8.3633","article-title":"AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1","volume":"94","author":"Hirota","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0092-8674(90)90801-K","article-title":"Signal transduction by receptors with tyrosine kinase activity","volume":"61","author":"Ullrich","year":"1990","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1096\/fasebj.9.9.7601337","article-title":"The MAPK signaling cascade","volume":"9","author":"Seger","year":"1995","journal-title":"FASEB J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1006\/exer.2002.1168","article-title":"Studies of the Mitogen-activated Protein Kinases and Phosphatidylinositol-3-kinase in the Lens: 1. The Mitogenic stress responses","volume":"74","author":"Zatechka","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1006\/exer.2002.2018","article-title":"Studies of the Mitogen-activated Protein Kinases and Phosphatidylinositol-3-kinase in the Lens: 2. The Intercommunications","volume":"75","author":"Zatechka","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1126\/science.2981433","article-title":"Prooxidant states and tumor promotion","volume":"227","author":"Cerutti","year":"1985","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0092-8674(94)90544-4","article-title":"H2O2 from the oxidative burst orchestrates the plants hypersensitive disease resistance response","volume":"79","author":"Levine","year":"1994","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/0891-5849(94)00198-S","article-title":"Superoxide and hydrogen peroxide in relation to mammalian cell proliferation","volume":"18","author":"Burdon","year":"1995","journal-title":"Free Radic. Bio. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S0955-0674(98)80147-6","article-title":"Oxygen radicals and signaling","volume":"10","author":"Finkel","year":"1998","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1042\/bj2630539","article-title":"Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha","volume":"263","author":"Meier","year":"1989","journal-title":"Biochem. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1083\/jcb.126.4.1079","article-title":"Production of hydrogen peroxide by transforming growth factor-beta 1 and its involvement in induction of egr-1 in mouse osteoblastic cells","volume":"126","author":"Ohba","year":"1994","journal-title":"J. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.270.5234.296","article-title":"Requirement for generation of H2O2-for platelet-derived growth factor signal transduction","volume":"270","author":"Sundaresan","year":"1995","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1074\/jbc.270.20.11727","article-title":"Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes","volume":"270","author":"Lo","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_82","first-page":"3413","article-title":"Expression of platelet-derived growth factor receptors in the developing chicken lens","volume":"35","author":"Potts","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.exer.2004.02.004","article-title":"Platelet derived growth factor (PDGF)-induced reactive oxygen species in the Lens epithelial cells","volume":"78","author":"Chen","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"Finkel","year":"2000","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"24519","DOI":"10.1016\/S0021-9258(17)31418-7","article-title":"The respiratory burst oxidase","volume":"269","author":"Chanock","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1073\/pnas.94.8.3771","article-title":"Arachidonic acid activates c-jun-N-terminal kinase through NADPH oxidase in rabbit proximal tubular epithelial cells","volume":"94","author":"Cui","year":"1997","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"15703","DOI":"10.1074\/jbc.271.26.15703","article-title":"Reactive oxygen species mediate cytokine activation of c-Jun NH2-terminal kinases","volume":"271","author":"Lo","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_88","first-page":"112","article-title":"Expression of nonphagocytic NADPH oxidase system in the ocular lens","volume":"10","author":"Rao","year":"2004","journal-title":"Mol. Vis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/0955-0674(93)90116-8","article-title":"Arachidonic acid in cell signaling","volume":"5","author":"Piomelli","year":"1993","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_90","first-page":"821","article-title":"The positive feedback role of arachidonic acid in platelet derived growth factor-induced cell signaling in lens epithelial cells","volume":"12","author":"Zhang","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_91","first-page":"374","article-title":"Control of PDGF-induced reactive oxygen species (ROS) generation and signal transduction in human lens epithelial cells","volume":"13","author":"Chen","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1167\/iovs.08-2568","article-title":"The Regulation of NADPH Oxidase and its Association with Cell Proliferation in Human Lens Epithelial Cells","volume":"50","author":"Wang","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"8231","DOI":"10.1167\/iovs.11-7542","article-title":"Regulation of cytosolic phospholipase A2 (cPLA2 alpha) and its association with cell proliferation in human lens epithelial cells","volume":"52","author":"Wang","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7696","DOI":"10.1073\/pnas.90.16.7696","article-title":"The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells","volume":"90","author":"Pepperkok","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"668","DOI":"10.3171\/jns.2002.97.3.0668","article-title":"Evidence for phosphatidylinositol 3-kinase-Akt-p7S6K pathway activation and transduction of mitogenic signals by platelet-derived growth factor in meningioma cells","volume":"97","author":"Johnson","year":"2002","journal-title":"J. Neurosurg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0960-9822(95)00080-7","article-title":"PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3-kinase","volume":"5","author":"Hawkins","year":"1995","journal-title":"Curr. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1182\/blood.V93.5.1464","article-title":"NADPH oxidase: An update","volume":"93","author":"Babior","year":"1999","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1161\/01.RES.86.5.494","article-title":"NAD(P)H oxidase: Role in cardiovascular biology and disease","volume":"86","author":"Griendling","year":"2000","journal-title":"Circ. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0014-5793(00)01669-0","article-title":"Redox-dependent signal transduction","volume":"476","author":"Finkel","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_100","first-page":"545","article-title":"Low molecular weight protein tyrosine phosphatase (LMW-PTP) and its possible physiological functions in the eye lens","volume":"1774","author":"Xing","year":"2007","journal-title":"Biochem. Biophys. Acta"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0968-0004(96)10059-1","article-title":"Structure and function of the protein tyrosine phosphatase","volume":"21","author":"Fauman","year":"1996","journal-title":"Trends Biochem. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.abb.2004.05.024","article-title":"Redox regulation of protein-tyrosine phosphatases","volume":"434","author":"Groen","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s00018-002-8481-z","article-title":"Low molecular weight protein tyrosine phosphatase: Small, but smart","volume":"59","author":"Raugei","year":"2002","journal-title":"Cell Mol. Life Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/jcp.1041650217","article-title":"A high phosphotyrosine phosphatase activity is present in differentiating bovine lens cells","volume":"165","author":"Blanquet","year":"1995","journal-title":"J. Cell Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/exer.2001.1018","article-title":"18kDa protein tyrosine phosphatase in the ocular lens","volume":"73","author":"Umeda","year":"2001","journal-title":"Exp. Eye Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1006\/geno.1995.9893","article-title":"Gene structure, sequence, and chromosomal localization of the human red cell-type low-molecular-weight acid phosphotyrosyl phosphatase gene, ACP1","volume":"30","author":"Bryson","year":"1995","journal-title":"Genomics"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0014-5793(98)00308-1","article-title":"Expression, purification and preliminary crystal analysis of the human low Mr phosphotyrosine protein phosphatase isoform 1","volume":"426","author":"Marzocchini","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_108","unstructured":"Lou, M.F., Xing, K.Y., Fernando, M.R., Moon, S., and Ho, Y.S. (2004). Thioltransferase knockout mouse: A new cataract model. Investig. Ophthalmol. Vis. Sci., 45."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1167\/iovs.07-1404","article-title":"Effect of thioltransferase (glutaredoxin) deletion on cellular sensitivity to oxidative stress and cell proliferation in lens epithelial cells of thioltransferase knockout mouse","volume":"49","author":"Lofgren","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.exer.2009.07.020","article-title":"Absence of glutaredoxine1 increases susceptibility to oxidative stress induced by UVR-B","volume":"89","author":"Meyer","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1167\/iovs.11-8504","article-title":"Protective effect of the thioltransferase gene on in vivo UVR-300 nm-induced cataract","volume":"53","author":"Kronschlager","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6598","DOI":"10.1167\/iovs.10-5672","article-title":"Effect of age on thioltransferase (glutaredoxin) and thioredoxin systems in the human lens","volume":"51","author":"Xing","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1167\/iovs.14-15452","article-title":"Loss of thiol repair systems in human cataractous lenses","volume":"56","author":"Wei","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.exer.2009.07.012","article-title":"Reactive oxygen species (ROS) are essential mediators in epidermal growth factor (EGF)-stimulated corneal epithelial cell proliferation, adhesion, migration, and wound healing","volume":"89","author":"Huo","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1167\/iovs.10-5866","article-title":"Low levels of hydrogen peroxide can stimulate corneal epithelial cell adhesion, migration and wound healing","volume":"52","author":"Pan","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"30374","DOI":"10.1074\/jbc.M100020200","article-title":"Identification and characterization of a new mammalian mitochondrial glutaredoxin (thioltransferase)","volume":"276","author":"Gladyshav","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_117","first-page":"1705","article-title":"Glutaredoxin2 prevents H2O2-induced cell apoptosis by protecting complex I activity","volume":"1797","author":"Wu","year":"2010","journal-title":"Biochem. Biophys. Acta"},{"key":"ref_118","unstructured":"Lou, M.F., Basu, S., Yu, Y., Wu, H., and Menko, A.S. (2012). Glutaredoxin2 (Grx2) gene knockout suppresses fiber cell differentiation and delays de-nucleation of the mouse lens. Investig. Ophthalmol. Vis. Sci., 53."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.exer.2007.05.001","article-title":"Regulation of thioredoxin by a specific thioredoxin-binding protein in the eye lens","volume":"85","author":"Liyanage","year":"2007","journal-title":"Exp. Eye Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/10\/1973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:45:16Z","timestamp":1760143516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/10\/1973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":119,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["antiox11101973"],"URL":"https:\/\/doi.org\/10.3390\/antiox11101973","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}