No abstract

Although supplemental oxygen is required to promote survival of severely premature infants, hyperoxia is simultaneously harmful to premature developing tissues such as in the retina.Here we report the effect of hyperoxia on central carbon metabolism in primary mouse Müller glial cells and a human Müller glia cell line (M10-M1 cells). We found decreased flux from glycolysis entering the tricarboxylic acid cycle in Müller cells accompanied by increased glutamine consumption in response to hyperoxia. In hyperoxia, anaplerotic catabolism of glutamine by Müller cells increased ammonium release two-fold. Hyperoxia induces glutamine-fueled anaplerosis that reverses basal Müller cell metabolism from production to consumption of glutamine.

3OH-pyruvate is a unique metabolite induced by hyperoxia that destabilizes HIF at least in part by a canonical pathway. 3OH-pyruvate induces angiostasis in vitro. HIF stabilization increases serine biosynthesis in vitro and in vivo.