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Methylglyoxal, a Metabolite Derived from Glycolysis, Functions as a Signal Initiator of the High Osmolarity Glycerol-Mitogen-activated Protein Kinase Cascade and Calcineurin/Crz1-mediated Pathway in Saccharomyces cerevisiae

Laboratory of Molecular Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Journal of Biological Chemistry (Impact Factor: 4.57). 02/2005; 280(1):253-60. DOI: 10.1074/jbc.M408061200
Source: PubMed

ABSTRACT Methylglyoxal (MG) is a typical 2-oxoaldehyde derived from glycolysis, although it inhibits the growth of cells in all types of organism. Hence, it has been questioned why such a toxic metabolite is synthesized via the ubiquitous energy-generating pathway. We have previously reported that expression of GLO1, coding for the major enzyme detoxifying MG, was induced by osmotic stress in a high osmolarity glycerol (HOG)-mitogen-activated protein (MAP) kinase-dependent manner in Saccharomyces cerevisiae. Here we show that MG activates the HOG-MAP kinase cascade. Two osmosensors, Sln1 and Sho1, have been identified to function upstream of the HOG-MAP kinase cascade, and we reveal that MG initiates the signal transduction to this MAP kinase cascade through the Sln1 branch. We also demonstrate that MG activates the Msn2 transcription factor. Moreover, MG activated the uptake of Ca(2+) in yeast cells, thereby stimulating the calcineurin/Crz1-mediated Ca(2+) signaling pathway. We propose that MG functions as a signal initiator in yeast.

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    • "Methyglyoxal and glyoxal inhibit yeast growth MG is a potent inhibitor of yeast growth (Aguilera and Prieto 2001; Aguilera et al. 2005; Bito et al. 1997; Inoue and Kimura 1996; Inoue et al. 1998; Maeta et al. 2005). Using a quantitative fitness assay, we quantified the growth inhibition for MG and glyoxal (Figure 1A). "
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    • "It reacts with cellular macromolecules (DNA, proteins) to form advanced glycation products and thereby affects the function of these molecules (Fleming et al. 2008; reviewed by Kalapos 2008; reviewed by Rabbani and Thornalley 2008). Methylglyoxal may also be involved in the generation of free radicals (reviewed by Kalapos 2008) and in cell signaling (Maeta et al. 2005). "
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    • "In order to test the putative involvement of C. lusitaniae Sho1p in resistance toward various drugs, we first tested the effect of methylglyoxal, a metabolic by-product whose toxic action on cells can be counteracted by triggering activation of the HOG signalling pathway (Aguilera et al., 2005; Maeta et al., 2005). The sensitivity toward this compound was similar in sho1 and wild-type cells (data not shown). "
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