Glyoxalase activity during differentiation of human leukaemia cells in vitro.
The activities of glyoxalase I and glyoxalase II were determined in human promyelocytic leukaemia HL60 and erythroleukaemia K562 cells in culture. The activity of glyoxalase I is ca 10-20 times greater than the activity of glyoxalase II under assay conditions. When HL60 and K562 cell lines were incubated with N-methylformamide and 8-carbamoyl-3-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045), substantial changes in the glyoxalase activities were induced. With HL60 cells, treatment with N-methylformamide and CCRG 81045, both of which induce functional differentiation of this cell line, there is a dose-dependent decrease in glyoxalase I activity and a concomitant dose-dependent increase in glyoxalase II activity, both of which are directly proportional to the number of differentiated cells. With K562 cells, N-methylformamide and CCRG 81045 induce an increase in both glyoxalase I and glyoxalase II activities, although only CCRG 81045 induces the appearance of haemoglobin producing cells. N-Methylformamide and CCRG 81045 do not activate or inhibit the activities of glyoxalase I and glyoxalase II from HL60 and K562 cells when studied in cell-free systems. The changes in the glyoxalase activities of HL60 and K562 cells during the incubations therefore appear to be due to alteration in the synthesis and/or regulatory modification of the glyoxalase enzymes induced by N-methylformamide and CCRG 81045. Despite the apparent disparity of the effect of differentiation on the glyoxalase system in the two cell lines, in both cases the glyoxalase I/glyoxalase II activity ratio decreases with the appearance of differentiated cells. Since glyoxalase II catalyses the rate-determining step in the glyoxalase system, this suggests that immature cells have an impaired capacity to metabolise S-D-lactoylglutathione.
D002454:Cell Differentiation; D003606:Dacarbazine / Q000031:analogs & derivatives*; D005559:Formamides / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology*; D008190:Lyases / Q000378:metabolism*; D000077204:Temozolomide; D013869:Thiolester Hydrolases / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology; D000099301:Hydroxyacylglutathione Hydrolase
D003606:Dacarbazine; D005559:Formamides; D007093:Imidazoles; D007791:Lactoylglutathione Lyase; D008190:Lyases; D000077204:Temozolomide; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C002950:methylformamide