We previously showed that treatment with bacterial lipopolysaccharide (LPS) or pro-inflammatory cytokines decreases NO-sensitive guanylyl cyclase (GCNO) activity in astrocytes by decreasing the half-life of the obligate GCNO β1 subunit in a NO-independent but transcription- and translation-dependent process. Here we show that LPS-induced β1 degradation requires proteasome activity and is independent of NFκB activation or β1 interaction with HSP90. Immunocytochemistry and confocal microscopy analysis revealed that LPS promotes colocalization of the predominantly soluble β1 protein with ubiquitin and the 20S proteasome in nuclear aggregates that present characteristics of clastosomes, nuclear bodies involved in proteolysis via the ubiquitin-proteasome system. Proteasome and protein synthesis inhibitors prevented LPS-induced clastosome assembly and nuclear colocalization of β1 with ubiquitin and 20S proteasome, strongly supporting a role for these transient nuclear structures in GCNO down-regulation during neuroinflammation. © 2007 Elsevier Inc. All rights reserved.
|Journal||Molecular and Cellular Neurosciences|
|Publication status||Published - 1 Mar 2008|
- NO-sensitive Guanylyl cyclase