title: Glutamine effect on cultured granule neuron death induced by glucose deprivation and chemical hypoxia.
abstract: Using a specific fluorescent probe of mitochondrial membrane potential (tetramethylrhodamine ethyl ester), we have shown that glucose deprivation (GD) of cultured cerebellar granule neurons (CGN) for 3 h lowers mitochondrial membrane potential in these cells. Longer glucose starvation (24 h) causes CGN death that is not prevented by blockers of ionotropic glutamate receptors (MK-801 (10 µM) and NBQX (10 µM)). Glutamine or pyruvate (2 mM) maintain membrane potential of mitochondria and decrease CGN death under GD conditions. In the presence of glucose the mitochondrial respiratory chain blocker rotenone induces neuron death potentiated by glutamine. The potentiation effect is completely prevented by blockers of ionotropic glutamate receptors. These results show that glutamine under conditions of GD can be utilized by mitochondria as substrate, but at the same time, in the case of mitochondrial function deterioration, metabolism of this amino acid results in glutamate accumulation to toxic level.
authors.affiliation: Department of Brain Research, Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, 105064, Russia. estelmash@mail.ru
authors.forename: E V
authors.initials: EV
authors.lastname: Stelmashook
authors.forename: S V
authors.initials: SV
authors.lastname: Novikova
authors.forename: N K
authors.initials: NK
authors.lastname: Isaev
mesh_terms: D000818:Animals; D016923:Cell Death; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000502:physiology*; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D019289:Pyruvic Acid / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058468:Receptors, Ionotropic Glutamate / Q000378:metabolism
chemical_list: D058468:Receptors, Ionotropic Glutamate; D005973:Glutamine; D019289:Pyruvic Acid; D005947:Glucose