Article: Apo J/clusterin expression and secretion: evidence for 15-deoxy-Δ(12,14)-PGJ(2)-dependent mechanism.
2012 Volume 1821, Issue 2, Page(s) 335–342
Abstract: Cyclooxygenase-2 (Cox-2) and Apo J/clusterin are involved in inflammatory resolution and have each been reported to inhibit NF-κB signalling. Using a well-validated rat pheochromocytoma (PC12) cell culture model of Cox-2 over-expression the current study ...
| Abstract | Cyclooxygenase-2 (Cox-2) and Apo J/clusterin are involved in inflammatory resolution and have each been reported to inhibit NF-κB signalling. Using a well-validated rat pheochromocytoma (PC12) cell culture model of Cox-2 over-expression the current study investigated inter-dependence between Cox-2 and clusterin with respect to induction of expression and impact on NF-κB signalling. Both gene expression and immunoblot analysis confirmed that intracellular and secreted levels of clusterin were elevated in Cox-2 over-expressing cells (PCXII). Clusterin expression was increased in control (PCMT) cells in a time- and dose-dependent manner by 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), but not PGE(2), and inhibited in PCXII cells by pharmacological Cox inhibition. In PCXII cells, inhibition of two transcription factors known to be activated by 15d-PGJ(2), heat shock factor 1 (HSF-1) and peroxisome proliferator activated receptor (PPAR)γ, by transcription factor oligonucleotide decoy and antagonist (GW9662) treatment, respectively, reduced clusterin expression. While PCXII cells exhibited reduced TNF-α-induced cell surface ICAM-1 expression, IkB phosphorylation and degradation were similar to control cells. With respect to the impact of Cox-2-dependent clusterin upregulation on NF-κB signalling, basal levels of IκB were similar in control and PCXII cells, and no evidence for a physical association between clusterin and phospho-IκB was obtained. Moreover, while PCXII cells exhibited reduced NF-κB transcriptional activity, this was not restored by clusterin knock-down. These results indicate that Cox-2 induces clusterin in a 15d-PGJ(2)-dependent manner, and via activation of HSF-1 and PPARγ. However, the results do not support a model whereby Cox-2/15d-PGJ(2)-dependent inhibition of NF-κB signalling involves clusterin. |
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| MeSH term(s) | Animals ; Clusterin/metabolism ; Clusterin/secretion ; Cyclooxygenase 2/metabolism ; DNA-Binding Proteins/metabolism ; Gene Knockdown Techniques ; Heat Shock Transcription Factors ; Intercellular Adhesion Molecule-1/metabolism ; Isopropyl Thiogalactoside/pharmacology ; NF-kappa B/metabolism ; PC12 Cells ; PPAR gamma/metabolism ; Prostaglandin D2/analogs & derivatives ; Prostaglandin D2/metabolism ; Rats ; Signal Transduction/drug effects ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; Tumor Necrosis Factor-alpha/pharmacology ; Up-Regulation/drug effects |
| Chemical Substances | 15-deoxy-delta(12,14)-prostaglandin J2 ; Clusterin ; DNA-Binding Proteins ; Heat Shock Transcription Factors ; NF-kappa B ; PPAR gamma ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Intercellular Adhesion Molecule-1 (126547-89-5) ; Isopropyl Thiogalactoside (367-93-1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Ptgs2 protein, rat (EC 1.14.99.1) ; Prostaglandin D2 (RXY07S6CZ2) |
| Language | English |
| Publishing date | 2012-02 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 60-7 |
| ISSN | 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399 |
| ISSN (online) | 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 |
| ISSN | 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399 |
| DOI | 10.1016/j.bbalip.2011.11.004 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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