The effect of albumin on astrocyte energy metabolism is not brought about through the control of cytosolic Ca2+ concentrations but by free-fatty acid sequestration.
Albumin is an important serum protein that under normal circumstances is not present in the brain. However, during development, under hypoxia, or after breakdown of the blood-brain barrier, albumin is found in the brain, where it is able to regulate energy metabolism. In this work the mechanism through which albumin regulates astrocyte metabolism was investigated. Our results show that albumin strongly increases (more than 100%) the flux of glucose and lactate through the pyruvate dehydrogenase-catalyzed reaction in astrocytes from primary culture. However, albumin only slightly stimulated other metabolic pathways, such as the tricarboxylic acid cycle or the pentose phosphate shunt, indicating that it exerts its effect specifically on the reaction catalyzed by pyruvate dehydrogenase. Although albumin increased cytosolic Ca2+ concentrations in astrocytes, our results show that the increase in pyruvate dehydrogenase activity promoted by albumin is not due to the enhancement of Ca2+ concentrations. Indeed, highly purified albumins failed to increase the Ca2+ concentration but did enhance lactate oxidation. In agreement with this, the effect of albumin on lactate oxidation was not abolished after Ca2+ depletion. Instead, the presence of fatty acids inhibited lactate oxidation and counteracted the effect of albumin, suggesting that albumin activates pyruvate dehydrogenase by binding free fatty acids and/or their CoA-derivatives.
Tabernero
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Departamento de Bioquimica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, Spain.
Medina
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Sánchez-Abarca
L I
LI
Lavado
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Medina
J M
JM
D000418:Albumins / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000418:Albumins; D005230:Fatty Acids, Nonesterified; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose; D002118:Calcium