Pathophysiological role of the glyoxalase system in renal hypoxic injury.
Methylglyoxal (MG), a reactive dicarbonyl compound mainly produced by metabolic pathways, such as glycolysis, binds to proteins or nucleic acids and forms advanced glycation end products. MG is efficiently metabolized by the glyoxalase system where MG is converted by glyoxalase I (GLO I) to S-D-lactoylglutathione. Although the glyoxalase system has been shown to play a pathological role in various diseases, including diabetic complications, its detailed pathophysiological function remains to be elucidated. We are interested in renal hypoxic diseases, but very little information is available regarding the association between the glyoxalase system and renal hypoxic diseases. Therefore, we investigated the biological role of GLO I in renal hypoxic diseases by using the rat ischemia/reperfusion (I/R) injury model. I/R induced the reduction of renal GLO I activity associated with morphological changes and renal dysfunction. Interestingly, the rats that overexpress human GLO I (GLO I Tg rats) showed amelioration of these manifestations in renal I/R (e.g., improvement of the tubulointerstitial injury and renal function). Accumulation of renal MG adducts, carboxyethyllysine, induced by I/R also decreased in GLO I Tg rats compared to wild-type rats. These results demonstrate that GLO I has renoprotective effects in I/R injury via reduction of protein modification by MG.
Kumagai
Takanori
T
Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
Nangaku
Masaomi
M
Inagi
Reiko
R
D058186:Acute Kidney Injury / Q000201:enzymology / Q000503:physiopathology* / Q000517:prevention & control; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000201:enzymology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism / Q000633:toxicity
D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase