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| Reference : Peroxisome proliferator-activated receptor-gamma1 is dephosphorylated and degraded durin... |
| Scientific journals : Article | |||
| Human health sciences : Rheumatology | |||
| http://hdl.handle.net/2268/94560 | |||
| Peroxisome proliferator-activated receptor-gamma1 is dephosphorylated and degraded during BAY 11-7085-induced synovial fibroblast apoptosis | |
| English | |
| Relic, Biserka [Université de Liège - ULg > > Rhumatologie >] | |
| Benoit, Valerie [ > > ] | |
| Franchimont, Nathalie [ > > ] | |
Kaiser, Marie-Joëlle  [Université de Liège - ULg > > Rhumatologie >] | |
| Hauzeur, Jean-Philippe [Université de Liège - ULg > > Rhumatologie >] | |
| Gillet, Philippe [Université de Liège - ULg > > Chirurgie appareil locomoteur >] | |
| Merville, Marie-Paule [Université de Liège - ULg > Département de pharmacie > Chimie médicale >] | |
| Bours, Vincent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Génétique générale et humaine >] | |
| Malaise, Michel [Université de Liège - ULg > Département des sciences cliniques > Rhumatologie >] | |
| 2006 | |
| Journal of Biological Chemistry | |
| American Society for Biochemistry and Molecular Biology | |
| 281 | |
| 32 | |
| 597-604 | |
| International | |
| 0021-9258 | |
| 1083-351X | |
| Baltimore | |
| MD | |
| [en] Apoptosis ; Cell Line ; Cell Nucleus ; Fibroblasts ; Gene Expression ; Nitriles ; Osteoarthritis ; Phosphorylation ; Prostaglandin D2 | |
| [en] Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a central
role in whole body metabolism by regulating adipocyte differentiation and energy storage. Recently, however, PPAR-gamma has also been demonstrated to affect proliferation, differentiation, and apoptosis of different cell types. As we have previously shown that BAY 11-7085-induced synovial fibroblast apoptosis is prevented by PPAR-gamma agonist 15d-PGJ2; the expression of PPAR-gamma in these cells was studied. Both PPAR-gamma1 and PPAR-gamma2 isoforms were cloned from synovial fibroblast RNA, but only PPAR-gamma1 was detected by Western blot, showing constitutive nuclear expression. Within minutes of BAY 11-7085 treatment, a PPAR-gamma1-specific band was shifted into a form of higher mobility, suggesting dephosphorylation, as confirmed by phosphatase treatment of cell extracts. Of interest, BAY 11-7085-induced PPAR-gamma1 dephosphorylation was followed by PARP and caspase-8 cleavage as well as by PPAR-gamma1 protein degradation. PPAR-gamma1 dephosphorylation was followed by the loss of PPAR-DNA binding activity ubiquitously present in synovial fibroblast nuclear extracts. Unlike the phosphorylated form, dephosphorylated PPAR-gamma1 was found in insoluble membrane cell fraction and was not ubiquitinated before degradation. PPAR-gamma1 dephosphorylation coincided with ERK1/2 phosphorylation that accompanies BAY 11-7085-induced synovial fibroblasts apoptosis. 15d-PGJ2, PGD2, and partially UO126, down-regulated ERK1/2 phosphorylation, protected cells from BAY 11-7085-induced apoptosis, and reversed both PPAR-gamma dephosphorylation and degradation. Furthermore, PPAR-gamma antagonist BADGE induced PPAR-gamma1 degradation, ERK1/2 phosphorylation, and synovial fibroblasts apoptosis. The results presented suggest an anti-apoptotic role for PPAR-gamma1 in synovial fibroblasts. Since apoptotic marker PARP is cleaved after PPAR-gamma1 dephosphorylation but before PPAR-gamma1 degradation, dephosphorylation event might be enough to mediate BAY 11-7085-induced apoptosis in synovial fibroblasts. | |
| Researchers ; Professionals | |
| http://hdl.handle.net/2268/94560 |
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