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R. H. Nagaraj, M. Staniszewska, A. Biswas, H. Butler, L. Reneker; Over-Expression of Glyoxalase I Inhibits AGE Formation in the Mouse Lens. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3183. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Methylglyoxal (MGO) is a reactive alpha-dicarbonyl compound formed from metabolic pathways in tissues. It reacts with proteins to form advanced glycation endproduct (AGE) adducts that can crosslink proteins. Glyoxalase, which is comprised of glyoxalase I and glyoxalase II catalyzes the conversion of MGO to D-lactate, thus it may negatively regulate protein modifications by MGO. Here we tested the role of glyoxalase I in prevention of AGE formation in transgenic mouse lenses.
Transgenic mice over-expressing glyoxalase I in the lens epithelium and fiber cells were developed by insertion of minigene containing human glyoxalase I and a chick delta1-crystallin enhancer/alphaA-crystallin promoter (Reneker et al., IOVS, 45: 4083-, 2004). Lenses from transgenic and wild type mice were organ-cultured with control media or media supplemented with DL-glyceraldehyde (GLD) for 48 hrs. Methylglyoxal (MGO) and AGEs, pentosidine and argpyrimidine were quantified by HPLC.
Transgenic animals expressed 25-30-fold higher levels of glyoxalase I in the lens. Glyoxalase I over-expression occurred both in the epithelium and cortical fiber cells in the lens. Lens organ culture in the presence of GLD (a precursor of MGO) resulted in cataract formation in wild type lenses, but not in glyoxalase I over-expressing lenses. Organ-culture with GLD enhanced the MGO content by ~13-fold in the wild type but only ~6-fold in glyoxalase I over-expressing lenses. The argpyrimidine content was increased by ~14-fold in GLD incubated wild type lenses but in glyoxalase I over-expressing lenses it was almost similar to untreated control lenses. The pentosidine content was higher in GLD treated wild type lenses but was suppressed in GLD treated lenses from transgenic animals.
Our study provides direct evidence that glyoxalase I plays an important role in controlling formation of AGEs in the lens.
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