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Titolo:
REGULATION OF ENERGY-METABOLISM IN SYNAPTIC TERMINALS AND CULTURED RAT-BRAIN ASTROCYTES - DIFFERENCES REVEALED USING AMINOOXYACETATE
Autore:
MCKENNA MC; TILDON JT; STEVENSON JH; BOATRIGHT R; HUANG S;
Indirizzi:
UNIV MARYLAND,SCH MED,DEPT PEDIAT,10-035 BRB,655 W BALTIMORE ST BALTIMORE MD 21201 UNIV MARYLAND,SCH MED,DEPT BIOL CHEM BALTIMORE MD 21201
Titolo Testata:
Developmental neuroscience
fascicolo: 3-5, volume: 15, anno: 1993,
pagine: 320 - 329
SICI:
0378-5866(1993)15:3-5<320:ROEIST>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIPPOCAMPAL SLICE PREPARATION; METHYLENE-DL-ASPARTATE; OXIDATIVE-METABOLISM; GLUTAMATE METABOLISM; AMINO-ACIDS; LACTATE-DEHYDROGENASE; PYRUVATE-CARBOXYLASE; ALPHA-KETOGLUTARATE; ISOENZYME PATTERN; NEURONS;
Keywords:
AMINOOXYACETIC ACID; ASTROCYTE; ENERGY METABOLISM; GLUCOSE; GLUTAMINE; 3-HYDROXYBUTYRATE; LACTATE; MALATE; METABOLIC REGULATION; SYNAPTOSOMES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
67
Recensione:
Indirizzi per estratti:
Citazione:
M.C. Mckenna et al., "REGULATION OF ENERGY-METABOLISM IN SYNAPTIC TERMINALS AND CULTURED RAT-BRAIN ASTROCYTES - DIFFERENCES REVEALED USING AMINOOXYACETATE", Developmental neuroscience, 15(3-5), 1993, pp. 320-329

Abstract

Several recent studies have demonstrated that the metabolism of energy substrates takes place in multiple compartments in both astrocytes and synaptic terminals from brain. There are a number of differences inthe metabolism of astrocytes and synaptic terminals primarily due to the localization of key enzymes such as pyruvate carboxylase and glutamine synthetase in astrocytes. The present study determined the rates of (CO2)-C-14 production from several energy substrates by primary cultures of astrocytes and cortical synaptic terminals from rat brain. The rates of (CO2)-C-14 production from labelled substrates by astrocytes were 0.96 +/- 0.13, 11.13 +/- 0.67, 10.51 +/- 0.35, 24.92 +/- 1.66 and 4.80 +/- 0.50 for D-[6-C-14]glucose, L-[U-C-14]lactate, D-3-hydroxy[3-C-14]butyrate, L-[U-C-14]glutamine and L-[U-C-14]ma-late, respectively. The rates of (CO2)-C-14 production were also measured in the presence of 5 mM aminooxyacetate (AOAA) to determine the effect of inhibiting the malate-aspartate shuttle and other transaminase reactions on the oxidation of energy substrates. In astrocytes the addition of AOAA decreased the rate of glutamine oxidation 5-fold, consistent with other studies showing that glutamine enters the TCA cycle via transamination. AOAA increased the rate of (CO2)-C-14 production from labelled glucose 4-fold, suggesting that inhibition of alanine biosynthesis profoundly alters the utilization of glucose by astrocytes. AOAA also increased the oxidation of lactate and 3-hydroxybutyrate 36 and 58%, respectively. The rates of (CO2)-C-14 production from labelled substrates by synaptic terminals were 13.12 +/- 1.05, 35.29 +/- 3.58, 17.66 +/- 1.95, 30.18 +/- 1.10 and 9.95 +/- 1.29, respectively, for glucose, lactate, 3-hydroxybutyrate, glutamine and malate, demonstrating that all substrates were oxidized at a higher rate by synaptic terminals than by astrocytes. The addition of AOAA decreased the rate of (CO2)-C-14 production from labelled lactate by 57% suggesting that the use of lactate for energy in synaptic terminals is tightly coupled to the activity of the malate-aspartate shuttle. AOAA had no effect on the rate of (CO2)-C-14 production from labelled glutamine, demonstrating that exogenous glutamine enters the TCA cycle in synaptic terminals via glutamate dehydrogenase, not via transamination as is the case with astrocytes. AOAA had no significant effect on the rates of oxidation of glucose, 3-hydroxybutyrate and malate by synaptic terminals. These findings demonstrate that inhibiting transamination with AOAA had very different effects on the oxidation of energy substrates in the two preparations, suggesting that the regulation of metabolism is quite different in astrocytes and synaptic terminals. These studies also underscore the importance of utilizing multiple energy substrates since the presence of AOAA altered energy metabolism in some, but not all, compartments of TCA cycle activity in both astrocytes and synaptic terminals.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 12:43:00