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Open Access Extracellular methylglyoxal toxicity in Saccharomyces cerevisiae: role of glucose and phosphate ions

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Abstract 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 andd-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.
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Keywords: AGE; glycation; glyoxalase; methylglyoxal; yeast

Document Type: Research Article

Publication date: 01 April 2008

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