Molecular basis for increased lactate formation in the Müller glial cells of retina.
KF, Ola MS, LaNoue . 2019
Müller glial cells are highly metabolic active cells that compensate for the high energy demand of retinal neurons. It has been believed that glucose provides the energy needs by the complete oxidation within Müller cells. However, numerous studies indicated that glial cells convert the majority of glucose to lactate, which may serve as an energy source for neurons. It is still not well understood why within glia, glucose is not completely oxidized under aerobic glycolysis conditions. The aspartate glutamate carrier (AGC) is a major component of the malate-aspartate shuttle (MAS) responsible for transporting the reducing equivalent of glycolysis to the mitochondria for the complete oxidation of glucose. Here, we report the absence of AGC within Müller glial cells which impairs the ability to oxidize glucose. We investigated the expression and localization of AGC and its isoforms (aralar and citrin) in the intact rat retina. We also analyzed the expression and regulation of AGC and its metabolic activity within cultured Müller cells (TR-MUL). The results suggest that AGC and its isoforms seem to be neuronal, with no or low expression within Müller cells of the intact retina. The study of cultured Müller cells suggests a very low expression of AGC and a decreased metabolic activity of the carrier especially under cell differentiation conditions due to low serum and hydrocortisone treatments. Thus, these data give a molecular explanation of increased levels of lactate formation due to a lack of AGC in the retina by Müller glial cells.
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