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Beta-amyloid peptides decrease soluble guanylyl cyclase expression in astroglial cells.

María Antonia Baltrons·Carlos E Pedraza·Michael T Heneka·Agustina García
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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.

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3',5'-Cyclic-GMP PhosphodiesterasesAmyloid beta-PeptidesAnimalsAstrocytesCells, CulturedCerebellumCyclic GMPCycloheximideEnzyme InductionGuanylate CyclaseIsoenzymesNerve Tissue ProteinsNitric OxideNitric Oxide DonorsNitritesNitroprussidePeptide FragmentsProtein SubunitsProtein Synthesis InhibitorsRNA, MessengerRatsRats, Sprague-DawleyReceptors, Cytoplasmic and NuclearSolubilitySoluble Guanylyl CyclaseJournal ArticleResearch Support, Non-U.S. Gov't

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María Antonia Baltrons, Carlos E Pedraza, Michael T Heneka, Agustina García. 2002. Beta-amyloid peptides decrease soluble guanylyl cyclase expression in astroglial cells.. https://doi.org/10.1006/nbdi.2002.0492

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