Fructose‐1,6‐diphosphate reduces cellular ROS level through up‐regulation of pentose phosphate pathway in BV‐2 microglia.

Abstract

Fructose-1,6-disphosphate(F1,6DP), a glycolytic intermediate, is known to have protective activities against ischemia/reperfusion injury and septic shock induced by bacterial lipopolysacharide(LPS). In the previous report, we have shown that F1,6DP could reduce LPS-induced iNOS expression and NO production in BV-2 mouse microglia. In consideration of the importance of ROS contribution to LPS-stimulated iNOS expression and NO production in BV-2 cells, we hypothesized that F1,6DP's anti-inflammatory effects would be due to ROS inhibition by up-regulation of pentose phosphate pathway(PPP), which is one of the most important antioxidative mechanisms. Upon investigation, we confirmed that LPS-induced ROS production in BV-2 cells was significantly reduced by F1,6DP(10mM). We found that F1,6DP enhanced LPS-induced activity of glucose-6-phopsphate dehydrogenase(G6PD), the key enzyme of PPP, even in a comparatively short time in the presence or absence of glucose. Interestingly, F1,6DP further increased LPS-stimulated G6PD expression in the levels of mRNA and protein. In consideration of PPP as one of the most important ROS scavenging mechanism, these data suggest that F1,6DP can reduce the cellular ROS generation by increasing metabolic flux through PPP, that is, by providing the substrate for G6PD, and by its up-regulating effect on G6PD expression. The research was supported by the “GRRC” Project of Gyeonggi Provincial Government, Republic of Korea.