The role of glyoxalase system in renal hypoxia.
Methylglyoxal (MG), a highly reactive alpha-oxoaldehyde generated by oxidation of carbohydrate and glycolysis, binds to proteins and forms advanced glycation end products (AGE). MG and MG adducts have been implicated in oxidative stress-related diseases, therefore, MG detoxifying system such as the glyoxalase system (glyoxalase I) also contributes to progression of these diseases. Recent papers have emphasized the pathophysiological effects of MG and the glyoxalase system in acute hypoxic injury, which is associated with acute oxidative stress. We investigated the kinetics of MG level and glyoxalase I activity in renal acute hypoxic injury induced by ischemia-reperfusion (I/R). I/R induced tubulointerstitial injury and the histological changes were associated with a significant decrease in renal glyoxalase I activity and an increase in MG level in the damaged tubular cells. Of note, rats over expressing human glyoxalase I showed amelioration of I/R-induced histological and functional damages and it was associated with a decrease in MG level in the lesion resulting in reduction of oxidative stress and tubular cell apoptosis. In conclusion, glyoxalase I has renoprotective effects in renal hypoxia such as I/R injury via a reduction in cytotoxic MG level in tubular cells.
Inagi
Reiko
R
Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. inagi-npr@umin.ac.jp
Kumagai
Takanori
T
Fujita
Toshiro
T
Nangaku
Masaomi
M
D000818:Animals; D006031:Glycosylation; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000201:enzymology* / Q000503:physiopathology / Q000517:prevention & control; D008658:Inactivation, Metabolic; D007674:Kidney Diseases / Q000150:complications* / Q000201:enzymology* / Q000503:physiopathology / Q000517:prevention & control; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism; D051381:Rats
D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase