Reference : Restoration of SHIP-1 activity in human leukemic cells modifies NF-kappaB activation ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Restoration of SHIP-1 activity in human leukemic cells modifies NF-kappaB activation pathway and cellular survival upon oxidative stress.
Gloire, Geoffrey mailto [Université de Liège - ULiège > > Virologie - Immunologie >]
Charlier, Edith mailto [Centre Hospitalier Universitaire de Liège - CHU > > Rhumatologie >]
Rahmouni, Souad mailto [Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation >]
Volanti, Cédric [> > > >]
Chariot, Alain [Centre Hospitalier Universitaire de Liège - CHU > > Chimie médicale >]
Erneux, Christophe [> > > >]
Piette, Jacques mailto [Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie - GIGA-Research >]
Nature Publishing Group
Yes (verified by ORBi)
United Kingdom
[en] Apoptosis/drug effects ; Blotting, Western ; Cell Survival/drug effects ; Flow Cytometry ; Genetic Complementation Test ; Humans ; Hydrogen Peroxide/pharmacology ; I-kappa B Kinase/metabolism ; I-kappa B Proteins/metabolism ; Jurkat Cells ; NF-kappa B/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phosphoric Monoester Hydrolases/genetics/metabolism ; Phosphorylation ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha/pharmacology ; Vanadates/pharmacology
[en] Nuclear factor-kappa B (NF-kappaB) is an important prosurvival transcription factor activated in response to a large array of external stimuli, including reactive oxygen species (ROS). Previous works have shown that NF-kappaB activation by ROS involved tyrosine phosphorylation of the inhibitor IkappaBalpha through an IkappaB kinase (IKK)-independent mechanism. In the present work, we investigated with more details NF-kappaB redox regulation in human leukemic cells. By using different cell lines (CEM, Jurkat and the subclone Jurkat JR), we clearly showed that NF-kappaB activation by hydrogen peroxide (H2O2) is cell-type dependent: it activates NF-kappaB through tyrosine phosphorylation of IkappaBalpha in Jurkat cells, whereas it induces an IKK-mediated IkappaBalpha phosphorylation on S32 and 36 in CEM and Jurkat JR cells. We showed that this H2O2-induced IKK activation in CEM and Jurkat JR cells is mediated by SH2-containing inositol 5'-phosphatase 1 (SHIP-1), a lipid phosphatase that is absent in Jurkat cells. Indeed, the complementation of SHIP-1 in Jurkat cells made them shift to an IKK-dependent mechanism upon oxidative stress stimulation. We also showed that Jurkat cells expressing SHIP-1 are more resistant to H2O2-induced apoptosis than the parental cells, suggesting that SHIP-1 has an important role in leukemic cell responses to ROS in terms of signal transduction pathways and apoptosis resistance, which can be of interest in improving ROS-mediated chemotherapies.
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