Albumin promotes neuronal survival by increasing the synthesis and release of glutamate.
It is well known that the presence of albumin within the brain and the CSF is developmentally regulated. However, the physiological relevance of this phenomenon is not well established. We have previously shown that albumin specifically increases the flux of glucose and lactate through the pyruvate dehydrogenase reaction in astrocytes. Here we show that, in neurones, albumin also increases the oxidation of glucose and lactate through the pyruvate dehydrogenase-catalysed reaction, the final purpose of this being the synthesis of glutamate. Thus, in neurones, the presence of albumin strongly increased the synthesis and release of glutamate to the extracellular medium. Our results also suggest that glutamate release caused by albumin is designed to promote neuronal survival. Thus, under culture conditions in which neurones die by apoptosis, the presence of albumin promoted neuronal survival and maintained the differentiation programme of these cells, as judged by the expression of the axonal protein, GAP-43. The effect of albumin on neuronal survival was counteracted by the presence of DNQX, an antagonist of non-NMDA-glutamate receptors, suggesting that the glutamate synthesized and released due to the presence of albumin is responsible for neuronal survival. In addition, the effect of albumin seemed to depend on the activity of the NGF receptor, TrkA, suggesting that the glutamate synthesized and released due to the presence of albumin promotes neuronal survival through the activity of TrkA.
Tabernero
Arantxa
A
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Hospital Universitario de Salamanca, Plaza de los Doctores de la Reina s/n, 37007 Salamanca, Spain.
Granda
Begoña
B
Medina
Ana
A
Sánchez-Abarca
Luis Ignacio
LI
Lavado
Eva
E
Medina
José M
JM
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019922:GAP-43 Protein / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D019922:GAP-43 Protein; D011810:Quinoxalines; D012709:Serum Albumin; D019344:Lactic Acid; D018698:Glutamic Acid; C056723:FG 9041; D020917:Receptor, trkA; D005947:Glucose