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

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 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.

Plasma advanced glycation end-products and skin autofluorescence are increased in COPD

“…It is known that the three AGEs that we measured in our study have distinct functionalities; pentosidine as a major cross-linking AGE, CML as a major ligand for the AGE receptor, and, importantly, CEL as a putative marker for intracellular glycation. Interestingly, the precursor molecule for CEL [24], methylglyoxal, is a highly reactive compound causing cell death [25].…”

D‐Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae

“…Cells were grown in 0.5%, 2% or 5% glucose SD medium for 6 h. The cells were permeabilized with digitonin to a final concentration of 0.05% and assayed for enzymatic activity using the procedures reported for glyoxalase I (Ispolnov et al, 2008) and aldose reductase (Gomes et al, 2005). For glyoxalase I assays, 5 mM GSH was mixed with 2 mM methylglyoxal and incubated for 10 min at 30 C to generate substrate.…”

The role of glyoxalases for sugar stress and aging, with relevance for dyskinesia, anxiety, dementia and Parkinson's disease

“…A stress-protection effect of glyoxalase I overexpression or a sensitizing effect of glyoxalase I deficiency was alredy documented in the bacteria Escherichia coli under anaerobic conditions with high carbon flux [16], the protozoan parasite Leishmania donovani [17], in the yeast Saccharomyces cerevisiae [18], in the plant Nicotiana tabacum [19,20], in the worm Caenorhabditis elegans [21] and in Rattus norvegicus and Homo sapiens under diabetic sugar stress [22,23]. …”