Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells
| العنوان: | Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells |
|---|---|
| المؤلفون: | Belén Mollá, Marta Casado, Rafael Mayoral, Lisardo Boscá, Paloma Martín-Sanz, Amalia Fernández-Martínez |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Biochemical Society, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Prostaglandin, Caspase 3, Apoptosis, Caspase 8, Biochemistry, Gene Expression Regulation, Enzymologic, Cell Line, S Phase, Hydrodynamic transfection, medicine, Humans, Hepatocyte, Molecular Biology, Caspase, biology, Cytochrome c, Intrinsic apoptosis, Cell Biology, Molecular biology, medicine.anatomical_structure, Liver, Cyclooxygenase 2, Hepatocytes, biology.protein, Cyclo-oxygenase (COX), Antibody, Biomarkers, Research Article |
| الوصف: | Copyright © by Portland Press. The final version of record is available at http://www.biochemj.org/bj/default.htmTest We have investigated the mechanism of COX-2 (cyclo-oxygenase 2)-dependent inhibition of apoptosis in liver, a key pathway underlying proliferative actions of COX-2 in liver cancers, cirrhosis, chronic hepatitis C infection and regeneration after partial hepatectomy. Stable expression of COX-2 in CHL (Chang liver) cells induced proliferation, with an increase in the proportion of cells in S-phase, but no other significant changes in cell-cycle distribution. This was associated with a marked inhibition of the apoptotic response to serum deprivation, an effect mimicked by treating empty-vector-transfected control cells (CHL-V cells) with prostaglandin E2 and prevented in COX-2-expressing cells (CHL-C cells) treated with selective inhibitors of COX-2. Serum-deprived CHL-V cells displayed several indicators of activation of intrinsic apoptosis: caspases 9 and 3 activated within 6 h and caspase 8 within 18 h, Bax expression was induced, cytochrome c was released to the cytosol, and PARP-1 [poly(ADP-ribose) polymerase 1] cleavage was evident in nuclei. COX-2 expression blocked these events, concomitant with reduced expression of p53 and promotion of Akt phosphorylation, the latter indicating activation of survival pathways. CHL cells were resistant to stimulation of the extrinsic pathway with anti-Fas antibody. Moreover, in vivo expression of GFP (green fluorescent protein)-labelled COX-2 in mice by hydrodynamics-based transient transfection conferred resistance to caspase 3 activation and apoptosis induced by stimulation of Fas. A. F. M. and R. M. were supported by CNIC (Centro Nacional de Investigaciones Cardiovasculares)/Bancaja fellowships. This work was supported by grants SAF2003-00342, SAF2004-00957 and SAF2005-03022 from CICYT (Comisión Interministerial de Ciencia y Tecnología), Spain and by a grant from Instituto de Salud Carlos III (Red de Centros C03/01). |
| وصف الملف: | 874243 bytes; application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfec0e42efc79c535dc2d9df15b2696dTest http://hdl.handle.net/10261/3588Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bfec0e42efc79c535dc2d9df15b2696d |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |