Interleukin-1β and lipopolysaccharide decrease soluble guanylyl cyclase in brain cells:: NO-independent destabilization of protein and NO-dependent decrease of mRNA

被引:22
作者
Pedraza, CE
Baltrons, MA
Heneka, MT
García, A [1 ]
机构
[1] Univ Autonoma Barcelona, Inst Biotecnol & Biomed V Villar Palasi, Bellaterra 08193, Spain
[2] Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Bellaterra 08193, Spain
[3] Univ Bonn, Dept Neurol, D-53105 Bonn, Germany
关键词
astroglia; nitric oxide; cGMP; soluble guanylyl cyclase; lipopolysaccharide; interleukin-1; beta;
D O I
10.1016/j.jneuroim.2003.08.034
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-a 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. (C) 2003 Elsevier B.V All rights reserved.
引用
收藏
页码:80 / 90
页数:11
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