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  • Poster presentation
  • Open Access

LPS-induced down-regulation of NO-sensitive guanylyl cyclase in astrocytes occurs by proteasomal degradation in nuclear bodies

  • 1Email author,
  • 1,
  • 2,
  • 2 and
  • 1
BMC Pharmacology20077 (Suppl 1) :P3

  • Published:


  • Guanylyl Cyclase
  • Nuclear Body
  • Calpain Inhibitor
  • Soluble Guanylyl Cyclase
  • Proteasome Inhibitor MG132


We have previously shown that inflammatory agents (LPS, IL-1β, β-amyloid peptides) that induce reactivity and NOS-2 expression in glial cells down-regulate astroglial soluble guanylyl cyclase (sGC) in vitro and in vivo [1, 2].


Here we show that the decrease in sGC activity and β1 subunit protein induced by LPS (10 ng/ml, 24 h) in cultured rat cerebellar astrocytes is prevented by inhibitors of proteasome activity (MG132 5 μM; lactacystin 10 μM) whereas other protease inhibitors (calpain inhibitor 25 μM; ICE inhibitor II 100 μM and leupeptin 5 μM) were not effective. Furthermore, immunocytochemistry and confocal laser microscopy revealed that in LPS-treated cells a strong sGC β1 immunorreactivity is evident in aggregates in the cell nuclei where it co-localizes with 20S proteasomes and ubiquitin in clastosomes, nucleoplasmic substructures involved in ubiquitin-proteasome-dependent nuclear proteolysis, but do not colocalize with others proteasome-enriched structures include promyelocytic leukaemia bodies and splicing speckles. In contrast, in untreated astrocytes clastosomes are scarce and sGC β1 immunorectivity shows a diffuse cytoplasmic pattern, while in the nucleus it is very weak. A similar distribution is observed when cells are treated with LPS and the proteasome inhibitor MG132 or the protein synthesis inhibitor cycloheximide.


LPS orchestrates the recruitment of sGC-β1 protein and components of the ubiquitin-proteasome system to specialized nuclear bodies, clastosomes, suggesting a mechanism for inflammation-induced down-regulation of sGC in astrocytes.



This work was supported by a SAF2004-01717 grant (Spain).

Authors’ Affiliations

Institute of Biotechnology and Biomedicine and Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Spain
Department of Anatomy and Cell Biology and Biomedicine Unit, CSIC, University of Cantabria, Spain


  1. Baltrons MA, Pedraza CE, Heneka MT, García A: β-Amyloid peptides decrease soluble guanylyl cyclase expression in astroglial cells. Neurobiol Dis. 2002, 10: 39-149. 10.1006/nbdi.2002.0492.View ArticleGoogle Scholar
  2. Pedraza CE, Baltrons MA, Heneka MT, García A: Interleukin-1β and lipopolysaccharide decrease soluble guanylyl cyclase in cells of the CNS: NO-independent destabilization of protein and NO-dependent decrease of mRNA. J Neuroimmunol. 2003, 144: 80-90. 10.1016/j.jneuroim.2003.08.034.View ArticlePubMedGoogle Scholar


© Baltrons et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.