Role of GLUT1 in regulation of reactive oxygen species

Abstract

In skeletal muscle cells, GLUT1 is responsible for a large portion of basal uptake of glucose and dehydroascorbic acid, both of which play roles in antioxidant defense. We hypothesized that conditions that would decrease GLUT1-mediated transport would cause increased reactive oxygen species (ROS) levels in L6 myoblasts, while conditions that would increase GLUT1-mediated transport would result in decreased ROS levels. We found that the GLUT1 inhibitors fasentin and phloretin increased the ROS levels induced by antimycin A and the superoxide generator pyrogallol. However, indinavir, which inhibits GLUT4 but not GLUT1, had no effect on ROS levels. Ataxia telangiectasia mutated (ATM) inhibitors and activators, previously shown to inhibit and augment GLUT1-mediated transport, increased and decreased ROS levels, respectively. Mutation of an ATM target site on GLUT1 (GLUT1-S490A) increased ROS levels and prevented the ROS-lowering effect of the ATM activator doxorubicin. In contrast, expression of GLUT1-S490D lowered ROS levels during challenge with pyrogallol, prevented an increase in ROS when ATM was inhibited, and prevented the pyrogallol-induced decrease in insulin signaling and insulin-stimulated glucose transport. Taken together, the data suggest that GLUT1 plays a role in regulation of ROS and could contribute to maintenance of insulin action in the presence of ROS.

Oxidative Stress during HIV Infection: Mechanisms and Consequences

“…The addition of GSH or GSH analogues is able to block late steps of viral replication [148], possibly by inhibiting the proper folding of glycosylated surface viral proteins in the ER, as was demonstrated for influenza virus [149]. The inhibitory effects of antioxidant treatment could also be attributed to the ability of ROS to induce CXCR4 receptor [150] as well as the glucose transporter Glut1 [151]. Enhanced expression of Glut1 was observed in both the infected cell cultures [152] and the neuronal tissues of the patients [153].…”

Mitochondrial control of cell bioenergetics in Parkinson’s disease

“…For instance, in skeletal muscle and cultured cells, H 2 O 2 stimulates glucose uptake [91–94]. Interestingly, in L6 myoblast, glucose uptake inhibition leads to increased ROS [95] and suggests a possible antioxidant-like role for glucose. Out of the 14 glucose transporter (GLUT) isoforms described so far [96], GLUT1 is up-regulated by ROS [97].…”

Inhibition of Glut1 by WZB117 sensitizes radioresistant breast cancer cells to irradiation

“…Moreover, a recent study described inhibition of Glut1 could increase ROS levels of myoblasts, suggesting that inhibition of Glut1 might modulate the radiosensitivity through the increased ROS [15]. In this study, we will investigate the roles of Glut1 in the radiosensitivity of human breast cancer.…”