Aim: The purpose of this study was to investigate the behaviour of Saccharomyces cerevisiae in response to extracellular methylglyoxal.

Methods and results: Cell survival to methylglyoxal and the importance of phosphates was investigated. The role of methylglyoxal detoxification systems and methylglyoxal-derived protein glycation were studied and the relation to cell survival or death was evaluated. Extracellular methylglyoxal decreased cell viability, and the presence of phosphate enhanced this effect. D-glucose seems to exert a protective effect towards this toxicity. Methylglyoxal-induced cell death was not apoptotic and was not related to intracellular glycation processes. The glyoxalases and aldose reductase were important in methylglyoxal detoxification. Mutants lacking glyoxalase I and II showed increased sensitivity to methylglyoxal, while strains overexpressing these genes had increased resistance.

Conclusions: Extracellular methylglyoxal induced non-apoptotic cell death, being unrelated to glycation. Inactivation of methylglyoxal-detoxifying enzymes by phosphate is one probable cause. Phosphate and D-glucose may also act through their complex involvement in stress response mechanisms.

Significance and impact of the study: These findings contribute to elucidate the mechanisms of cell toxicity by methylglyoxal. This information could be useful to on-going studies using yeast as a eukaryotic cell model to investigate methylglyoxal-derived glycation and its role in neurodegenerative diseases.

• PMID: 18194258
• DOI full text
• PubMed

Reference Type

Journal Article | Research Support, Non-U.S. Gov't

Authors

Ispolnov K, Gomes RA, Silva MS, Freire AP

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