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The effect of albumin on astrocyte energy metabolism is not brought about through the control of cytosolic Ca 2+ concentrations but by free‐fatty acid sequestration
Author(s) -
Tabernero Arantxa,
Medina Ana,
SánchezAbarca Luis Ignacio,
Lavado Eva,
Medina José M.
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(19990101)25:1<1::aid-glia1>3.0.co;2-2
Subject(s) - cytosol , biology , albumin , metabolism , astrocyte , energy metabolism , biochemistry , endocrinology , central nervous system , enzyme
Abstract 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 Ca 2+ concentrations in astrocytes, our results show that the increase in pyruvate dehydrogenase activity promoted by albumin is not due to the enhancement of Ca 2+ concentrations. Indeed, highly purified albumins failed to increase the Ca 2+ concentration but did enhance lactate oxidation. In agreement with this, the effect of albumin on lactate oxidation was not abolished after Ca 2+ 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. GLIA 25:1–9, 1999. © 1999 Wiley‐Liss, Inc.