Beta-amyloid peptides decrease soluble guanylyl cyclase expression in astroglial cells.
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.
Instituto de Biotecnología y Biomedicina V. Villar Palasi, Departamento de Bioquímica Biología Molecular, Universidad Autónoma de Barcelona, 08193, Bellaterra, Spain.
María Antonia
MA
Baltrons
Carlos E
CE
Pedraza
Michael T
MT
Heneka
Agustina
A
García
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000096:biosynthesis; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D006152:Cyclic GMP / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D021122:Protein Subunits; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D012995:Solubility; D000071756:Soluble Guanylyl Cyclase
D016229:Amyloid beta-Peptides; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D009573:Nitrites; D010446:Peptide Fragments; D021122:Protein Subunits; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D009599:Nitroprusside; D009569:Nitric Oxide; D003513:Cycloheximide; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP