title: Short- and long-term enzymatic regulation secondary to metabolic insult in the rat retina.
abstract: Changes in oxygen and/or glucose availability may result in altered levels of ATP production and amino acid levels, and alteration in lactic acid production. However, under certain metabolic insults, the retina demonstrates considerable resilience and maintains ATP production, and/or retinal function. We wanted to investigate whether this resilience would be reflected in alterations in the activity of key enzymes of retinal metabolism, or enzymes associated with amino acid production that may supply their carbon skeleton for energy production. Enzymatic assays were conducted to determine the activity of key retinal metabolic enzymes total ATPase and Na(+)/K(+)-ATPase, aspartate aminotransferase and lactate dehydrogenase. In vitro anoxia led to an increase in retinal lactate dehydrogenase activity and to a decrease in retinal aspartate aminotransferase activity, without significant changes in Na(+)/K(+)-ATPase activity. In vivo inhibition of glutamine synthetase resulted in a short-term significant decrease in retinal aspartate aminotransferase activity. An increase in retinal aspartate aminotransferase and lactate dehydrogenase activities was accompanied by altered levels of amino acids in neurons and glia after partial inhibition of glial metabolism, implying that short- and long-term up- and down-regulation of key metabolic enzymes occurs to supply carbon skeletons for retinal metabolism. ATPase activity does not appear to fluctuate under the metabolic stresses employed in our experimental procedures.
authors.affiliation: Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Acosta
authors.forename: Michael
authors.initials: M
authors.lastname: Kalloniatis
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D002952:Citric Acid Cycle / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004798:Enzymes / Q000378:metabolism*; D005970:Glutamate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007003:Hypoglycemia / Q000201:enzymology* / Q000503:physiopathology; D045022:Lactate Dehydrogenases / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology* / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D004798:Enzymes; D018698:Glutamic Acid; D045022:Lactate Dehydrogenases; D005970:Glutamate Synthase; D001219:Aspartate Aminotransferases; D000254:Sodium-Potassium-Exchanging ATPase