[en] In astroglial cells beta-amyloid peptides (betaA) induce a reactive phenotype and increase expression of NO synthase. Here we show that treatment of rat brain astrocytes with betaA decreases their capacity to accumulate cyclic GMP (cGMP) in response to NO as a result of a decreased expression of soluble guanylyl cyclase (sGC) at the protein and mRNA levels. Potentiation of betaA-induced NO formation by interferon-gamma did not result in a larger decrease in cGMP formation and inhibition of NO synthase failed to reverse down-regulation of sGC, indicating that NO is not involved. The betaA effect was prevented by the protein synthesis inhibitor cycloheximide. Intracerebral betaA injection also decreased sGC beta1 subunit mRNA levels in adult rat hippocampus and cerebellum. A loss of sGC in reactive astrocytes surrounding beta-amyloid plaques could be a mechanism to prevent excess signalling via cGMP at sites of high NO production.
Disciplines :
Neurology
Author, co-author :
Baltrons, María Antonia; Instituto de Biotecnología y Biomedicina V. Villar Palasi, Departamento de Bioquímica Biología Molecular, Universidad Autónoma de Barcelona, 08193, Bellaterra, Spain
Pedraza, Carlos E; Instituto de Biotecnología y Biomedicina V. Villar Palasi, Departamento de Bioquímica Biología Molecular, Universidad Autónoma de Barcelona, 08193, Bellaterra, Spain
HENEKA, Michael ; Department of Neurology, University of Bonn, 53105, Bonn, Germany
García, Agustina; Instituto de Biotecnología y Biomedicina V. Villar Palasi, Departamento de Bioquímica Biología Molecular, Universidad Autónoma de Barcelona, 08193, Bellaterra, Spain
External co-authors :
yes
Language :
English
Title :
Beta-amyloid peptides decrease soluble guanylyl cyclase expression in astroglial cells.
We thank Francisca García for assistance in cell culture preparations and Annabel Segura for technical assistance. This work was supported in part by DGICYT (PB97-0201), Fundació La Marató TV3 (1008/97), and DGR (SGR99-00123) grants. Carlos E. Pedraza is the recipient of a predoctoral fellowship from Ministerio de Educación y Cultura (Spain).
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