title: Astrocyte glucose metabolism under normal and pathological conditions in vitro.
abstract: Astrocytes in primary culture produce lactate. The net production of lactate from glucose requires that the carbon flux through glycolysis exceed the carbon flux to CO2. This study investigates the control and function of this 'excess' glycolysis in astrocyte cultures. Blockade of glycolysis was found to have minimal effects on astrocyte ATP and function if other substrates for oxidative metabolism were available. In contrast, selective blockade of oxidative metabolism reduced adenosine triphosphate (ATP) levels and slowed glutamate uptake despite a marked increase in glycolytic rate. Acidosis suppressed both glucose utilization and lactate production but had minimal effects on ATP levels. Acidosis in combination with blockade of oxidative metabolism blunted the increase in glycolytic rate and accentuated ATP depletion relative to oxidative blockade alone. These studies suggest that glycolysis in astrocyte cultures is regulated by factors other than energy demand, and that the capacity of glycolysis to support astrocyte metabolism during hypoxia is markedly pH dependent.
authors.affiliation: Department of Neurology, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Swanson
authors.forename: J H
authors.initials: JH
authors.lastname: Benington
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001386:Azides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D000860:Hypoxia / Q000378:metabolism*; D019344:Lactic Acid / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
chemical_list: D001386:Azides; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D005947:Glucose