Interleukin-1 beta and lipopolysaccharide decrease soluble guanylyl cyclase in brain cells: NO-independent destabilization of protein and NO-dependent decrease of mRNA.
We previously showed that soluble guanylyl cyclase (sGC) is down-regulated in astroglial cells after exposure to LPS. Here, we show that this effect is not mediated by released IL-1beta but that this cytokine is also able to decrease NO-dependent cGMP accumulation in a time- and concentration-dependent manner. The effect of IL-1beta is receptor-mediated, mimicked by tumor necrosis factor-alpha and involves a decrease in sGC activity and protein. IL-1beta and LPS decrease the half-life of the sGC beta1 subunit by a NO-independent but transcription- and translation-dependent mechanism. Additionally, both agents induce a NO-dependent decrease of sGC subunit mRNA. Decreased sGC subunit protein and mRNA levels are also observed in adult rat brain after focal injection of IL-1beta or LPS.
Institute of Biotechnology and Biomedicine V. Villar Palasi, and Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Spain.
Carlos E
CE
Pedraza
María Antonia
MA
Baltrons
Michael T
MT
Heneka
Agustina
A
García
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000201:enzymology / Q000276:immunology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004795:Enzyme Stability / Q000235:genetics / Q000276:immunology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006207:Half-Life; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D014176:Protein Biosynthesis / Q000276:immunology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014158:Transcription, Genetic / Q000276:immunology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D021122:Protein Subunits; D012333:RNA, Messenger; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP