Induction of glutamine synthetase in embryonic neural retina: its suppression by the gliatoxic agent alpha-aminoadipic acid.
Competence for cortisol-mediated induction of glutamine synthetase (GS) is a differentiation marker of embryonic neural retina. Earlier work has indicated that the induction and accumulation of GS is localized in the Müller glia cells. This localization was presently confirmed by the finding that the gliatoxin D,L-alpha-amino-adipic acid (AAA) reduces responsiveness to GS induction by 60--90% due to preferential damage to Müller cells. The tests were performed on organ cultures of retina tissue from chick embryos, and on retina cell aggregates in which there is tissue reconstruction. The presence of GS-inducible Müller cells was monitored by immuno-staining of tissue sections with anti-GS antiserum. Reduction of GS inducibility due to pretreatment with AAA resulted in virtual absence of cells that immunostained for GS. The preferential toxicity of AAA for Müller cells was also demonstrated by cell viability tests; it was further corroborated by the finding that treatment with AAA greatly reduced the level of carbonic anhydrase activity, another enzyme localized predominantly in Müller cells, but did not affect gamma-aminobutyric acid transaminase and choline acetyl transferase, neuronal enzymes. Susceptibility of Müller cells to AAA was found to increase with embryonic development of the retina. We suggest that acquisition of susceptibility for AAA represents another differentiation marker of embryonic Müller cells.
D015074:2-Aminoadipic Acid / Q000494:pharmacology*; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D004790:Enzyme Induction / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis*; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000201:enzymology
D000600:Amino Acids, Dicarboxylic; D015074:2-Aminoadipic Acid; D005974:Glutamate-Ammonia Ligase