Regulation of glutamate metabolism by hydrocortisone and branched chain keto acids in cultured rat retinal Müller cells (TR-MUL)

► Cultured retinal Müller cells (TR-MUL) was found to be well differentiated. ► TR-MUL cells expressed GS, PC and BCATm involved in glutamate metabolism. ► Hydrocortisone increased amidation and BCKAs increased oxidation of glutamate. ► Amidation and oxidation pathways of glutamate disposal did not...

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Bibliographic Details
Published in:Neurochemistry international 2011-10, Vol.59 (5), p.656-663
Main Authors: Ola, Mohammad Shamsul, Hosoya, Ken-Ichi, LaNoue, Kathryn F.
Format: Article
Language:English
Subjects:
Amides - metabolism
Amino Acids, Branched-Chain - pharmacology
Animals
Biological and medical sciences
Blotting, Western
Cell Differentiation - drug effects
Cells, Cultured
Diabetes. Impaired glucose tolerance
Diabetic retinopathy
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Eye and associated structures. Visual pathways and centers. Vision
Fundamental and applied biological sciences. Psychology
Glutamate excitotoxicity
Glutamate-Ammonia Ligase - biosynthesis
Glutamate-Ammonia Ligase - metabolism
Glutamic Acid - metabolism
Glutamine synthetase
Hydrocortisone - pharmacology
Keto Acids - pharmacology
Medical sciences
Nerve Tissue Proteins - metabolism
Neurodegeneration
Neuroglia - drug effects
Neuroglia - metabolism
Neuroprotection
Oxidation-Reduction
Pyruvate Carboxylase - metabolism
Rats
Retina
Retina - cytology
Retina - drug effects
Retina - metabolism
Vertebrates: nervous system and sense organs
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Summary:► Cultured retinal Müller cells (TR-MUL) was found to be well differentiated. ► TR-MUL cells expressed GS, PC and BCATm involved in glutamate metabolism. ► Hydrocortisone increased amidation and BCKAs increased oxidation of glutamate. ► Amidation and oxidation pathways of glutamate disposal did not influence each other. ► Glutamate uptake increased when glutamate level was decreased within Müller cells. Glutamate released from retinal neurons during neurotransmission is taken up by retinal Müller cells, where much of the amino acid is subsequently amidated to glutamine or transaminated to α-ketoglutarate for oxidation. Müller cell glutamate levels may have to be carefully maintained at fairly low concentrations to avoid excesses of glutamate in extracellular spaces of the retina that would otherwise cause excitotoxicity. We employed a cultured rat retinal Müller cell line in order to study the metabolism and the role of Müller cell specific enzymes on the glutamate disposal pathways. We found that the TR-MUL cells express the glial specific enzymes, glutamine synthetase, the mitochondrial isoform of branched chain aminotransferase (BCATm) and pyruvate carboxylase, all of which are involved in glutamate metabolism and homeostasis in the retina. Hydrocortisone treatment of TR-MUL cells increased glutamine synthetase expression and the rate of glutamate amidation to glutamine. Addition of branched chain keto acids (BCKAs) increased lactate and aspartate formation from glutamate and also oxidation of glutamate to CO2 and H2O. The two glutamate disposal pathways (amidation and oxidation) did not influence each other. When glutamate levels were independently depleted within TR-MUL cells, the uptake of glutamate from the extracellular fluid increased compared to uptake from control (undepleted) cells suggesting that the level of intracellular glutamate may influence clearing of extracellular glutamate.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2011.06.010