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Regulation of glutamate metabolism by hydrocortisone and branched chain keto acids in cultured rat retinal Müller cells (TR-MUL).
MedLine Citation:
PMID:  21756956     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 CO(2) and H(2)O. 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.
Authors:
Mohammad Shamsul Ola; Ken-Ichi Hosoya; Kathryn F Lanoue
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-3
Journal Detail:
Title:  Neurochemistry international     Volume:  -     ISSN:  1872-9754     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
Department of Ophthalmology, College of Medicine, King Saud University, Old Airport Road, KAUH, Riyadh 11411, Saudi Arabia; Department of Cellular and Molecular Physiology, Penn-State College of Medicine, Hershey, PA 17033, USA.
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