Authors: Magdalena M Staniszewska Ram H Nagaraj
Publish Date: 2006/04/01
Volume: 288, Issue: 1-2, Pages: 29-36
Abstract
Glyoxalase I is the first enzyme in a twoenzyme glyoxalase system that metabolizes physiological methylglyoxal MGO MGO reacts with proteins to form irreversible adducts that may lead to crosslinking and aggregation of lens proteins in diabetes This study examined the effect of hyperglycemia on glyoxalase I activity and its mRNA content in mouse lens epithelial cells mLE cells and in diabetic mouse lenses and investigated the relationship between GSH and MGO in organ cultured lenses mLE cells cultured with 25 mM Dglucose high glucose showed an upregulation of glyoxalase I activity and a higher content of glyoxalase I mRNA when compared with either cells cultured with 5 mM glucose control or with 20 mM Lglucose + 5 mM Dglucose MGO concentration was significantly elevated in cells cultured with high Dglucose but not in Lglucose GSH levels were lower in cells incubated with high glucose compared to control cells Glyoxalase I activity and mRNA levels were elevated in diabetic lenses compared to nondiabetic control mouse lenses MGO levels in diabetic lenses were higher than in control lenses Incubation of lenses with buthionine sulfoximine BSO resulted in a dramatic decline in GSH but the MGO levels were similar to lenses incubated without BSO Our data suggest that in mouse lenses MGO accumulation may occur independent of GSH concentration and in diabetes there is an upregulation of glyoxalase I but this upregulation is inadequate to normalize MGO levels which could lead to MGO retention and chemical modification of proteins
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