Skip to main content

Advertisement

Log in

Glyoxalase I activity and immunoreactivity in the aging human lens

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Glyoxalase I (GLOI) is the first enzyme of the glyoxalase system that catalyzes the metabolism of reactive dicarbonyls, such as methylglyoxal (MGO). During aging and cataract development, human lens proteins are chemically modified by MGO, which is likely due to inadequate metabolism of MGO by the glyoxalase system. In this study, we have determined the effect of aging on GLOI activity and the immunoreactivity and morphological distribution of GLOI in the human lens. A monoclonal antibody was developed against human GLOI. GLOI immunoreactivity was strongest in the anterior epithelial cells and weaker in rest of the lens. Cultured human lens epithelial cells showed immunostaining throughout the cytoplasm. In the human lens, GLOI activity and immunoreactivity both decreased with age. We believe that this would lead to promotion of MGO-modification in aging lens proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahmed N, Thornalley PJ (2002) Chromatographic assay of glycation adducts in human serum albumin glycated in vitro by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and intrinsic fluorescence. Biochem J 364:15–24

    CAS  PubMed  Google Scholar 

  • Ahmed N, Thornalley PJ, Dawczynski J, Franke S, Strobel J, Stein G, Haik GM (2003) Methylglyoxal-derived hydroimidazolone advanced glycation end-products of human lens proteins. Invest Ophthalmol Vis Sci 44:5287–5292. doi:10.1167/iovs.03-0573

    Article  PubMed  Google Scholar 

  • Ahmed U, Dobler D, Larkin SJ, Rabbani N, Thornalley PJ (2008) Reversal of hyperglycemia-induced angiogenesis deficit of human endothelial cells by overexpression of glyoxalase 1 in vitro. Ann N Y Acad Sci 1126:262–264. doi:10.1196/annals.1433.035

    Article  CAS  PubMed  Google Scholar 

  • Bhat SP (2001) The ocular lens epithelium. Biosci Rep 21:537–563. doi:10.1023/A:1017952128502

    Article  CAS  PubMed  Google Scholar 

  • Biemel KM, Friedl DA, Lederer MO (2002) Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound. J Biol Chem 277:24907–24915. doi:10.1074/jbc.M202681200

    Article  CAS  PubMed  Google Scholar 

  • Chellan P, Nagaraj RH (1999) Protein crosslinking by the maillard reaction: dicarbonyl-derived imidazolium crosslinks in aging and diabetes. Arch Biochem Biophys 368:98–104. doi:10.1006/abbi.1999.1291

    Article  CAS  PubMed  Google Scholar 

  • David LL, Shearer TR (1989) Role of proteolysis in lenses: a review. Lens Eye Toxic Res 6:725–747

    CAS  PubMed  Google Scholar 

  • Degenhardt TP, Thorpe SR, Baynes JW (1998) Chemical modification of proteins by methylglyoxal. Cell Mol Biol Noisy-le-grand 44:1139–1145

    CAS  PubMed  Google Scholar 

  • de Hemptinne V, Rondas D, Vandekerckhove J, Vancompernolle K (2007) Tumour necrosis factor induces phosphorylation primarily of the nitric-oxide-responsive form of glyoxalase I. Biochem J 407:121–128. doi:10.1042/BJ20070379

    Article  PubMed  Google Scholar 

  • Fujiwara H, Takigawa Y, Suzuki T, Nakata K (1992) Superoxide dismutase activity in cataractous lenses. Jpn J Ophthalmol 36:273–280

    CAS  PubMed  Google Scholar 

  • Haik GM Jr, Lo TW, Thornalley PJ (1994) Methylglyoxal concentration and glyoxalase activities in the human lens. Exp Eye Res 59:497–500. doi:10.1006/exer.1994.1135

    Article  CAS  PubMed  Google Scholar 

  • Hovatta I, Tennant RS, Helton R, Marr RA, Singer O, Redwine JM, Ellison JA, Schadt EE, Verma IM, Lockhart DJ, Barlow C (2005) Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice. Nature 438:662–666. doi:10.1038/nature04250

    Article  CAS  PubMed  Google Scholar 

  • Jedziniak JA, Arredondo LM, Meys M (1986) Human lens enzyme alterations with age and cataract: glyceraldehyde-3-P dehydrogenase and triose phosphate isomerase. Curr Eye Res 5:119–126. doi:10.3109/02713688609015100

    Article  CAS  PubMed  Google Scholar 

  • Junaid MA, Kowal D, Barua M, Pullarkat PS, Sklower Brooks S, Pullarkat RK (2004) Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor. Am J Med Genet A 131:11–17. doi:10.1002/ajmg.a.30349

    Article  PubMed  Google Scholar 

  • Kawatani M, Okumura H, Honda K, Kanoh N, Muroi M, Dohmae N, Takami M, Kitagawa M, Futamura Y, Imoto M, Osada H (2008) The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I. Proc Natl Acad Sci USA 105:11691–11696. doi:10.1073/pnas.0712239105

    Article  CAS  PubMed  Google Scholar 

  • Kuhla B, Boeck K, Schmidt A, Ogunlade V, Arendt T, Munch G, Luth HJ (2007) Age- and stage-dependent glyoxalase I expression and its activity in normal and Alzheimer’s disease brains. Neurobiol Aging 28:29–41. doi:10.1016/j.neurobiolaging.2005.11.007

    Article  CAS  PubMed  Google Scholar 

  • Kumar MS, Reddy PY, Kumar PA, Surolia I, Reddy GB (2004) Effect of dicarbonyl-induced browning on alpha-crystallin chaperone-like activity: physiological significance and caveats of in vitro aggregation assays. Biochem J 379:273–282. doi:10.1042/BJ20031633

    Article  CAS  PubMed  Google Scholar 

  • Lou MF (2000) Thiol regulation in the lens. J Ocul Pharmacol Ther 16:137–148. doi:10.1089/jop.2000.16.137

    Article  CAS  PubMed  Google Scholar 

  • Mancini MA, Unakar NJ, Giblin FJ, Reddan JR (1989) Histochemical localization of catalase in cultured lens epithelial cells. Ophthalmic Res 21:369–373

    CAS  PubMed  Google Scholar 

  • Mannervik B (2008) Molecular enzymology of the glyoxalase system. Drug Metabol Drug Interact 23:13–27

    CAS  PubMed  Google Scholar 

  • Miller AG, Smith DG, Bhat M, Nagaraj RH (2006) Glyoxalase I is critical for human retinal capillary pericyte survival under hyperglycemic conditions. J Biol Chem 281:11864–11871. doi:10.1074/jbc.M513813200

    Article  CAS  PubMed  Google Scholar 

  • Mitsumoto A, Kim KR, Oshima G, Kunimoto M, Okawa K, Iwamatsu A, Nakagawa Y (2000) Nitric oxide inactivates glyoxalase I in cooperation with glutathione. J Biochem 128:647–654

    CAS  PubMed  Google Scholar 

  • Morcos M, Du X, Pfisterer F, Hutter H, Sayed AA, Thornalley P, Ahmed N, Baynes J, Thorpe S, Kukudov G, Schlotterer A, Bozorgmehr F, El Baki RA, Stern D, Moehrlen F, Ibrahim Y, Oikonomou D, Hamann A, Becker C, Zeier M, Schwenger V, Miftari N, Humpert P, Hammes HP, Buechler M, Bierhaus A, Brownlee M, Nawroth PP (2008) Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. Aging Cell 7:260–269. doi:10.1111/j.1474-9726.2008.00371.x

    Article  CAS  PubMed  Google Scholar 

  • Nagaraj RH, Oya-Ito T, Padayatti PS, Kumar R, Mehta S, West K, Levison B, Sun J, Crabb JW, Padival AK (2003) Enhancement of chaperone function of alpha-crystallin by methylglyoxal modification. Biochemistry 42:10746–10755. doi:10.1021/bi034541n

    Article  CAS  PubMed  Google Scholar 

  • Ornek K, Karel F, Buyukbingol Z (2003) May nitric oxide molecule have a role in the pathogenesis of human cataract? Exp Eye Res 76:23–27. doi:10.1016/S0014-4835(02)00268-3

    Article  CAS  PubMed  Google Scholar 

  • Oya T, Hattori N, Mizuno Y, Miyata S, Maeda S, Osawa T, Uchida K (1999) Methylglyoxal modification of protein. Chemical and immunochemical characterization of methylglyoxal-arginine adducts. J Biol Chem 274:18492–18502. doi:10.1074/jbc.274.26.18492

    Article  CAS  PubMed  Google Scholar 

  • Padayatti PS, Jiang C, Glomb MA, Uchida K, Nagaraj RH (2001a) High concentrations of glucose induce synthesis of argpyrimidine in retinal endothelial cells. Curr Eye Res 23:106–115. doi:10.1076/ceyr.23.2.106.5472

    Article  CAS  PubMed  Google Scholar 

  • Padayatti PS, Ng AS, Uchida K, Glomb MA, Nagaraj RH (2001b) Argpyrimidine, a blue fluorophore in human lens proteins: high levels in brunescent cataractous lenses. Invest Ophthalmol Vis Sci 42:1299–1304

    CAS  PubMed  Google Scholar 

  • Piec I, Listrat A, Alliot J, Chambon C, Taylor RG, Bechet D (2005) Differential proteome analysis of aging in rat skeletal muscle. FASEB J 19:1143–1145

    CAS  PubMed  Google Scholar 

  • Rathbun WB, Bovis MG (1986) Activity of glutathione peroxidase and glutathione reductase in the human lens related to age. Curr Eye Res 5:381–385. doi:10.3109/02713688609025177

    Article  CAS  PubMed  Google Scholar 

  • Reddan JR, Steiger CA, Dziedzic DC, Gordon SR (1996) Regional differences in the distribution of catalase in the epithelium of the ocular lens. Cell Mol Biol Noisy-le-grand 42:209–219

    CAS  PubMed  Google Scholar 

  • Rehnstrom K, Ylisaukko-Oja T, Vanhala R, von Wendt L, Peltonen L, Hovatta I (2008) No association between common variants in glyoxalase 1 and autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet 147:124–127. doi:10.1002/ajmg.b.30582

    Google Scholar 

  • Rulli A, Carli L, Romani R, Baroni T, Giovannini E, Rosi G, Talesa V (2001) Expression of glyoxalase I and II in normal and breast cancer tissues. Breast Cancer Res Treat 66:67–72. doi:10.1023/A:1010632919129

    Article  CAS  PubMed  Google Scholar 

  • Shamsi FA, Lin K, Sady C, Nagaraj RH (1998) Methylglyoxal-derived modifications in lens aging and cataract formation. Invest Ophthalmol Vis Sci 39:2355–2364

    CAS  PubMed  Google Scholar 

  • Shamsi FA, Sharkey E, Creighton D, Nagaraj RH (2000) Maillard reactions in lens proteins: methylglyoxal-mediated modifications in the rat lens. Exp Eye Res 70:369–380. doi:10.1006/exer.1999.0800

    Article  CAS  PubMed  Google Scholar 

  • Shang F, Gong X, Palmer HJ, Nowell TR Jr, Taylor A (1997) Age-related decline in ubiquitin conjugation in response to oxidative stress in the lens. Exp Eye Res 64:21–30. doi:10.1006/exer.1996.0176

    Article  CAS  PubMed  Google Scholar 

  • Shinohara M, Thornalley PJ, Giardino I, Beisswenger P, Thorpe SR, Onorato J, Brownlee M (1998) Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Invest 101:1142–1147. doi:10.1172/JCI119885

    Article  CAS  PubMed  Google Scholar 

  • Silva MS, Barata L, Ferreira AE, Romao S, Tomas AM, Freire AP, Cordeiro C (2008) Catalysis and structural properties of leishmania infantum glyoxalase II: trypanothione specificity and phylogeny. Biochemistry 47:195–204. doi:10.1021/bi700989m

    Article  CAS  PubMed  Google Scholar 

  • Spector A (1995) Oxidative stress-induced cataract: mechanism of action. FASEB J 9:1173–1182

    CAS  PubMed  Google Scholar 

  • Thornalley PJ (2003) Glyoxalase I–structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans 31:1343–1348. doi:10.1042/BST0311343

    Article  CAS  PubMed  Google Scholar 

  • Thornalley PJ (2007) Endogenous alpha-oxoaldehydes and formation of protein and nucleotide advanced glycation endproducts in tissue damage. Novartis Found Symp 285:229–243. doi:10.1002/9780470511848.ch17 (discussion 243-226)

    Article  CAS  PubMed  Google Scholar 

  • Wilker SC, Chellan P, Arnold BM, Nagaraj RH (2001) Chromatographic quantification of argpyrimidine, a methylglyoxal-derived product in tissue proteins: comparison with pentosidine. Anal Biochem 290:353–358. doi:10.1006/abio.2001.4992

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported from NIH grants R01EY-016219 and R01EY-09912 (RHN), P30EY-11373 (Visual Sciences Research Center of CWRU), Research to Prevent Blindness, NY, and the Ohio Lions Eye Research Foundation. We thank Catherine Doller at the Visual Sciences Research Center for help with immunostaining experiments and Santosh Kanade, Mahesha Gangadhariah for help with the GLOI activity assay.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ram H. Nagaraj.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mailankot, M., Padmanabha, S., Pasupuleti, N. et al. Glyoxalase I activity and immunoreactivity in the aging human lens. Biogerontology 10, 711–720 (2009). https://doi.org/10.1007/s10522-009-9218-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-009-9218-2

Keywords

Navigation