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Interleukin-1 beta and lipopolysaccharide decrease soluble guanylyl cyclase in brain cells: NO-independent
Carlos E Pedraza1, María Antonia Baltrons, Michael T Heneka
1Institute of Biotechnology and Biomedicine V. Villar Palasi, and Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Spain.
Abstract:
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.
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