TitleEvidence of high levels of methylglyoxal in cultured Chinese hamster ovary cells.
Publication TypeJournal Article
Year of Publication1998
AuthorsChaplen, FW, Fahl, WE, Cameron, DC
JournalProc Natl Acad Sci U S A
Volume95
Issue10
Pagination5533-8
Date Published1998 May 12
ISSN0027-8424
KeywordsAnimals, CHO Cells, Chromatography, High Pressure Liquid, Cricetinae, Female, Glycolysis, Ovary, Pyruvaldehyde, Quinoxalines
Abstract

Methylglyoxal is an alpha-ketoaldehyde and dicarbonyl formed in cells as a side product of normal metabolism. Endogenously produced dicarbonyls, such as methylglyoxal, are involved in numerous pathogenic processes in vivo, including carcinogenesis and advanced glycation end-product formation; advanced glycation end-products are contributors to the pathophysiology of aging and chronic diabetes. Despite recent advances in understanding of the systemic effects of methylglyoxal, the full significance of this compound remains unknown. Herein we provide evidence that the majority of the methylglyoxal present in vivo is bound to biological ligands. The basis for our finding is an experimental approach that provides a measure of the bound methylglyoxal present in living systems, in this instance Chinese hamster ovary cells; with our approach, as much as 310 microM methylglyoxal was detected, 100- to 1,000-fold more than observed previously in biological systems. Several artifacts were considered before concluding that the methylglyoxal was associated with cellular structures, including phosphate elimination from triose phosphates, carbohydrate degradation under the assay conditions, and interference from the derivatizing agent used as part of the assay procedure. A major source of the recovered methylglyoxal is most probably modified cellular proteins. With methylglyoxal at about 300 microM, 0.02% of cellular amino acid residues could be modified. As few as one or two "hits" with methylglyoxal per protein molecule have previously been reported to be sufficient to cause protein endocytosis and subsequent degradation. Thus, 5-10% of cellular proteins may be modified to physiologically significant levels.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID9576917
PubMed Central IDPMC20412
Grant ListP01-CA-22484 / CA / NCI NIH HHS / United States
T32 GM08349-03 / GM / NIGMS NIH HHS / United States