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Originally published In Press as doi:10.1074/jbc.M108760200 on November 27, 2001
J. Biol. Chem., Vol. 277, Issue 6, 4240-4246, February 8, 2002
Transcytosis of Albumin in Astrocytes Activates the
Sterol Regulatory Element-binding Protein-1, Which Promotes the
Synthesis of the Neurotrophic Factor Oleic Acid*
Arantxa
Tabernero §,
Ana
Velasco§¶,
Begoña
Granda,
Eva M.
Lavado , and
José M.
Medina**
From the Departamento de Bioquímica y Biología
Molecular, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain and the Unidad de Investigación,
Hospital Universitario de Salamanca, 37007 Salamanca, Spain
We have recently reported that albumin, a serum
protein present in the developing brain, stimulates the synthesis of
oleic acid by astrocytes, which promotes neuronal differentiation. In this work, we gain insight into the mechanism by which albumin induces
the synthesis of this neurotrophic factor. Our results show that
astrocytes internalize albumin in vesicle-like structures by
receptor-mediated endocytosis. Albumin uptake was followed by
transcytosis, including passage through the endoplasmic reticulum, which was required to induce the synthesis of oleic acid. Oleic acid
synthesis is feedback-regulated by the sterol regulatory element-binding protein-1, which induces the transcription of stearoyl-CoA 9-desaturase, the key rate-limiting enzyme for oleic acid
synthesis. In our research, the presence of albumin activated the
sterol regulatory element-binding protein-1 and increased stearoyl-CoA
9-desaturase mRNA. Moreover, when the activity of sterol regulatory
element-binding protein-1 was inhibited by overexpression of a
truncated form of this protein, albumin did not affect stearoyl-CoA 9-desaturase mRNA, indicating that the effect of albumin is
mediated by this transcription factor. The effect of albumin was
abolished when traffic to the endoplasmic reticulum was prevented or
when albumin was accompanied with oleic acid. In conclusion, our
results suggest that the transcytosis of albumin includes passage
through the endoplasmic reticulum, where oleic acid is sequestrated,
initiating the signal cascade leading to an increase in its own synthesis.
*
This work was supported by Fondo de Investigaciones
Sanitarias (Spain), Direccion General de Enseñanza Superior, and
the Junta de Castilla y León, Spain.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
These authors equally contributed to this work.
¶
A recipient of a Beca de Forracion en Investigacion fellowship
from the Fondo de Investigaciones Sanitarias.
A recipient of a fellowship from the University of Salamanca.
**
To whom correspondence should be addressed: Departamento de
Bioquímica y Biología Molecular, Universidad de
Salamanca, Edificio Departamental, Pza Doctores de la Reina s/n. 37007 Salamanca, Spain. Tel.: 34-923-29-45-26; Fax: 34-923-29-45-64; E-mail:
medina@usal.es.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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