Research Article

A potential protective role for thiamine in glucose-driven oxidative stress

Published: July 25, 2014
Genet. Mol. Res. 13 (3) : 5582-5593 DOI: 10.4238/2014.July.25.13

Abstract

The relationship between glucose repression and the oxidative stress response was investigated in Schizosaccharomyces pombe wild type cells (972h-) and glucose repression resistant mutant type cells (ird11). We aimed to reveal the mechanism of simultaneous resistance to glucose repression and oxidative stress in ird11 mutants. Compared to the wild type, the expression of the sty1 gene was not altered in the ird11 mutant under normal growth conditions, but decreased after exposure to H2O2. This effect was clearly explained by the immunoblotting results, which showed elevated levels of a much more stable phosphorylated form of Sty1 mitogen-activated protein kinase in the ird11 mutant. Increased ght3 gene expression levels were also found, which may play a role in protecting the ird11 mutant from the deleterious effects of oxidative stress. In addition, decreased expression levels of glycolytic enzyme enolase- and thiamine synthesis/transport-related genes were detected. This might have resulted from the flux redirection toward mitochondrial respiration, which would enhance NADPH generation to prevent the high reactive oxygen species accumulation that is generated by respiration. Some evidence supported a flux shift toward fermentation as well as respiration. We conclude that a defect in the glucose-sensing signaling pathway in ird11 mutants likely causes erroneous low glucose-sensing signaling and high ATP production. This most likely occurs because high glucose availability in the medium induces an impairment in the respiratory chain and fermentation balance in these cells, which might explain the glucose repression and oxidative stress resistance in ird11 compared to the wild type.

The relationship between glucose repression and the oxidative stress response was investigated in Schizosaccharomyces pombe wild type cells (972h-) and glucose repression resistant mutant type cells (ird11). We aimed to reveal the mechanism of simultaneous resistance to glucose repression and oxidative stress in ird11 mutants. Compared to the wild type, the expression of the sty1 gene was not altered in the ird11 mutant under normal growth conditions, but decreased after exposure to H2O2. This effect was clearly explained by the immunoblotting results, which showed elevated levels of a much more stable phosphorylated form of Sty1 mitogen-activated protein kinase in the ird11 mutant. Increased ght3 gene expression levels were also found, which may play a role in protecting the ird11 mutant from the deleterious effects of oxidative stress. In addition, decreased expression levels of glycolytic enzyme enolase- and thiamine synthesis/transport-related genes were detected. This might have resulted from the flux redirection toward mitochondrial respiration, which would enhance NADPH generation to prevent the high reactive oxygen species accumulation that is generated by respiration. Some evidence supported a flux shift toward fermentation as well as respiration. We conclude that a defect in the glucose-sensing signaling pathway in ird11 mutants likely causes erroneous low glucose-sensing signaling and high ATP production. This most likely occurs because high glucose availability in the medium induces an impairment in the respiratory chain and fermentation balance in these cells, which might explain the glucose repression and oxidative stress resistance in ird11 compared to the wild type.