Premium
Methylglyoxal accumulation by glutathione depletion leads to cell cycle arrest in Dictyostelium
Author(s) -
Choi ChangHoon,
Park SeongJun,
Jeong SunYoung,
Yim HyungSoon,
Kang SaOuk
Publication year - 2008
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2008.06497.x
Subject(s) - methylglyoxal , biology , glutathione , dithiothreitol , microbiology and biotechnology , dictyostelium discoideum , cell growth , biochemistry , dictyostelium , enzyme , gene
Summary Reduced glutathione (GSH) serves as a primary redox buffer and its depletion causes growth inhibition or apoptosis in many organisms. In Dictyostelium discoideum , the null mutant ( gcsA ‐ ) of gcsA encoding γ‐glutamylcysteine synthetase shows growth arrest and developmental defect when GSH is depleted. To investigate the mechanism by which GSH depletion induces growth arrest, a proteomic analysis was performed and aldose reductase (AlrA) was identified as the most prominently induced protein in gcsA ‐ cells. Induction of AlrA was dependent on GSH concentration and was repressed by GSH but not effectively by either the reducing agent such as dithiothreitol or overexpression of superoxide dismutase. Methylglyoxal (MG), a toxic α‐ketoaldehyde, strongly induced alrA expression and AlrA catalysed MG reduction efficiently. The alrA knockdown gcsA ‐ cells ( gcsA ‐ / alrA as ) exhibited more decreased growth rate than gcsA ‐ cells, whereas the gcsA ‐ cells overexpressing alrA ( gcsA ‐ / alrA oe ) showed the recovery of growth rate. Interestingly, intracellular MG levels were significantly augmented in gcsA ‐ / alrA as cells compared with gcsA ‐ cells following GSH depletion. By contrast, gcsA ‐ / alrA oe cells showed repression of MG induction. Furthermore, MG treatment inhibited growth of wild‐type KAx3 cells, inducing G1 phase arrest. Thus, our findings suggest that MG accumulated by GSH depletion inhibits cell growth in Dictyostelium .