2024-03-28T16:38:03Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/35882021-12-28T15:50:03Zcom_10261_86com_10261_1com_10261_109col_10261_339col_10261_362
2008-04-15T11:20:31Z
urn:hdl:10261/3588
Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells
Fernández-Martínez, Amalia
Mollá, Belén
Mayoral, Rafael
Boscá, Lisardo
Casado, Marta
Martín-Sanz, Paloma
Apoptosis
Cyclo-oxygenase (COX)
Hepatocyte
Hydrodynamic transfection
Liver
Prostaglandin
Copyright © by Portland Press. The final version of record is available at http://www.biochemj.org/bj/default.htm
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.
2008-04-15T11:20:31Z
2008-04-15T11:20:31Z
2006-08-29
artículo
Biochem J. 2006 September 15; 398(Pt 3): 371–380
1470-8728
http://hdl.handle.net/10261/3588
10.1042/BJ20060780
16800815
eng
openAccess
Biochemical Society