Peroxisome proliferator-activated receptor-gamma1 is dephosphorylated and degraded during BAY 11-7085-induced synovial fibroblast apoptosis

in Journal of Biological Chemistry (2006), 281(32), 597-604

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 ... [more ▼]

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. [less ▲]

Perpectives for Technology Assessment in Wallonia: a "Country" Case Study

Conference (2012, November 15)

Les perquisitions dans les cabinets d’avocats. Les usages à l’épreuve de la jurisrpudence de la Cour européenne des droits de l’homme

in Deruyck, Filip (Ed.) Het strafrecht bedreven, Liber amicorum Alain De Nauw (2011)

Confrontation de la législation et de la jurisprudence belges en matière de perquisition dans les cabinets d'avocat avec la jurisprudence de la Cour européenne des droits de l'homme

PERS - Doctoraat onderzoekt de kwaliteit van leven bij alzheimer

in Contactblad van het Academisch Centrum voor Huisartsgeneeskunde van de K.U.Leuven (2012)

Persistance des troubles psychologiques et comportementaux de la démence

Poster (2010, October)

est considérable. Actuellement, la sélection d’un traitement dépend de la nature du trouble et de son intensité. La connaissance de leur persistance s’avère importante pour la sélection et l’organisation ... [more ▼]

est considérable. Actuellement, la sélection d’un traitement dépend de la nature du trouble et de son intensité. La connaissance de leur persistance s’avère importante pour la sélection et l’organisation du traitement. Objectifs: Evaluer la persistance des troubles psychologiques et comportementaux dans une population de sujets déments suivis longitudinalement. Méthodes: Nous avons sélectionné 104 sujets déments issus de l’étude Qualidem (Paquay et al., 2004). Tous les sujets sont institutionnalisés et présentent des perturbations cognitives (score MMSE<20). Les troubles psychologiques et comportementaux ont été évalués à 12 mois d’intervalle avec le Neuropsychiatric Inventory (Cummings et al., 1997). Résultats: Les perturbations les plus persistantes sont les idées délirantes (62%), et l’agitation (67%). Le risque de rechute est moins important pour la dépression (54%), les hallucinations (44%), l’exaltation de l’humeur (43%), l’apathie (48%), l’irritabilité (52%), et le comportement moteur aberrant (52%). L’anxiété (38%), la désinhibition (39%), les troubles du sommeil (39%) et de l’appétit (38%) sont les moins persistants. Conclusion: La nature persistante de l’agitation et des idées délirantes suggère que le traitement de ces perturbations doit être prolongé. La nature ponctuelle de l’anxiété, la désinhibition et des troubles de l’appétit et du sommeil suggère qu’un traitement à court terme est plus approprié pour ces perturbations. Ces résultats sont à interpréter par rapport à la définition des troubles induite par le NPI. [less ▲]

Persistence of an intact endometrial matrix and vessels structure in women exposed to VA-2914, a selective progesterone receptor modulator.

in Journal of Clinical Endocrinology and Metabolism (2008), 93(11), 4525-31

Background: VA-2914 is a selective progesterone receptor modulator with potential contraceptive activity that induces amenorrhea, whereas progestins cause endometrial spotting and bleeding. This abnormal ... [more ▼]

Background: VA-2914 is a selective progesterone receptor modulator with potential contraceptive activity that induces amenorrhea, whereas progestins cause endometrial spotting and bleeding. This abnormal bleeding due to progestins is a consequence of focal stromal proteolysis by an increase in naked vessel size and density. Objective: Our objective was to quantify the effects of VA-2914 on endometrial vascularization, fibrillar matrix, and vascular endothelial growth factor (VEGF)-A expression in endometrial biopsies from 41 women before and after 12 wk daily treatment with a placebo, or 2.5, 5, or 10 mg VA-2914. Methods: Collagen fibrillar network was stained by silver impregnation. Vessel area, density, and structure were quantified with a computer-assisted image analysis system after double immunostaining using an anti-von Willebrand factor (endothelial cells) and an anti- smooth muscle actin (vascular smooth muscle cells) marker antibody. VEGF-A mRNAs were quantified by RT-PCR and localized by immunohistochemistry. Results: The endometrial vessels, collagen network, and mRNA levels of VEGF-A were identical during the luteal phase at baseline and in VA-2914 treated women. VEGF-A distribution was unchanged. Conclusions: VA-2914 does not alter the endometrial matrix and cells, and does not modify the endometrial vessel morphology as compared with baseline biopsies. [less ▲]

Persistence of Scattering Centers

Scientific conference (1993)

Persistent efficacy of moxidectin 1% injectable and 0.5% pour-on against natural Psoroptes ovis infestation in cattle

Conference (1997)

Persistent infection of thymic epithelial cells with coxsackievirus B4 results in a decreased expression of insulin-like growth factor 2

in Journal of Virology (2012), 86

It has been hypothesized that a disturbance of central self-tolerance to islet β-cell may play a role in the enteroviral pathogenesis of type 1 diabetes. Whether enteroviruses can induce an impaired ... [more ▼]

It has been hypothesized that a disturbance of central self-tolerance to islet β-cell may play a role in the enteroviral pathogenesis of type 1 diabetes. Whether enteroviruses can induce an impaired expression of β-cell self-antigens in thymic epithelial cells has been investigated in a murine thymic epithelial (MTE) cell line. This cell line was permissive to the diabetogenic strain CV-B4 E2 and spontaneously expressed type 2 insulin-like growth factor (Igf2), the dominant self-antigen of the insulin family. In this model, a persistent replication of CV-B4 E2 was obtained as attested by the prolonged detection of intracellular positive and negative-strand viral RNA by RT-PCR, and capsid protein VP1 by IF and by the release of infectious particles in culture supernatant fluids. The chronic stage of the infection was characterized by a low proportion of VP1-positive cells (1-2%) whereas many cells harbored enteroviral RNA as displayed by RT-PCR without extraction applied directly on a few cells. Igf2 mRNA and IGF-2 protein were dramatically decreased in CV-B4 E2-infected MTE cultures compared with mock-infected cultures, whereas housekeeping and Il6 genes expression were maintained and Igf1 mRNA was decreased but at a lower extent. Inoculation of CV-B3-, CV-B4 JVB- or Echovirus 1 resulted in a low level of IGF-2 in culture supernatant fluids as well, whereas HSV-1 stimulated the production of the protein. Thus, a persistent infection of a thymic epithelial cell line with enteroviruses, like CV-B4 E2 can result in a disturbed production of IGF-2, a protein involved in central self-tolerance towards islet β-cells. [less ▲]

Persistent Ischemic Mitral Regurgitation After Annuloplasty can be Predicted by Pre-operative Echocardiography.

Conference (2006)