Incidence and potential implications of the toxic metabolite methylglyoxal in cell culture: A review.

Cytotechnology
F W Chaplen

Abstract

Methylglyoxal is a toxic metabolite unavoidably produced in mammalian systems as a by-product of glycolysis. Detoxification of this compound occurs principally through the glyoxalase pathway, which consists of glyoxalase I and glyoxalase II, and requires reduced glutathione as a co-enzyme. Recently, it has been demonstrated that variations in glucose, glutamine and fetal bovine serum levels can cause significant changes in the intracellular concentration of methylglyoxal. More importantly, comparative studies involving wild-type Chinese hamster ovary cells and clones overexpressing glyoxalase I indicate that glucose and glutamine, within the range normally found in cell culture media, can cause decreased cell viability mediated solely through increased production of methylglyoxal. In addition, endogenously produced methylglyoxal has been shown to cause apoptosis in cultured HL60 cells. While the exact mechanism of the impact of methylglyoxal on cultured cells is unknown, methylglyoxal is a potent protein and nucleic acid modifying agent at physiological concentrations and under physiological conditions. Protein modification occurs mainly at arginine, lysine and cysteine residues and is believed to be an important signal for the...Continue Reading

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