Beta-amyloid peptides decrease soluble guanylyl cyclase expression in astroglial cells |
| |
Authors: | Baltrons María Antonia Pedraza Carlos E Heneka Michael T García Agustina |
| |
Institution: | Instituto de Biotecnología y Biomedicina V. Villar Palasi, Departamento de Bioquímica Biología Molecular, Universidad Autónoma de Barcelona, 08193, Bellaterra, Spain. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|