Inhibition of protein and DNA synthesis in tissue culture cells by a derivative of methyl glyoxal and ascorbate.
The inhibitory effect of a methyl glyoxal-ascorbate (MGA) adduct (NFCR 278021) on protein and DNA synthesis in monolayer cultures of GPK epithelial cells has been compared with the inhibitory action of methyl glyoxal (MG). GPK cells exhibited an ID50 of 0.98 microM MG for both protein and DNA synthesis compared with an ID50 of 0.92 mM for the adduct. Hill plots demonstrate that the characteristics of the receptor saturation are the same for MG and MGA, suggesting that the action of the two agents is mediated through the MG moiety which is modified by the presence of the ascorbate portion of the molecule in MGA. It is shown that MGA undergoes spontaneous oxidation in solution and is a substrate for ascorbate oxidase, but that no additional MG activity is released by total enzymic oxidation of MGA, and oxidised MGA possesses the same inhibitory characteristics as MGA. Inhibition of protein synthesis by ascorbate or dehydroascorbate were not demonstrated in the dose range employed for MGA. The inhibitory effect of the adduct on protein synthesis was found to be diminished in the presence of glutathione and glyoxalase I (Glo I) and II( Glo II).
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006168:Guinea Pigs; D007791:Lactoylglutathione Lyase / Q000494:pharmacology; D014176:Protein Biosynthesis; D011765:Pyruvaldehyde / Q000494:pharmacology*; D012867:Skin; D013869:Thiolester Hydrolases / Q000494:pharmacology; D000099301:Hydroxyacylglutathione Hydrolase
D000447:Aldehydes; D001205:Ascorbic Acid; D004247:DNA; D003683:Dehydroascorbic Acid; D005978:Glutathione; D007791:Lactoylglutathione Lyase; D011765:Pyruvaldehyde; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase