A Jurkat T cell variant resistant to death receptor-induced apoptosis. Correlation with heat shock protein (Hsp) 27 and 70 levels.
Ligation of Fas induces an apoptotic program in Jurkat cells (Jd). We describe a Jurkat T cell variant (Jr) which shows total resistance to Fas-mediated apoptosis but which exhibits sensitivity to non-death-receptor pro-apoptotic stimuli such as staurosporine. Resistance to Fas-induced apoptosis in Jr cells is correlated with high expression of Hsps. A prior heat-shock increases Hsp27 and 70 expression and protects Jd and Jr cells from Fas- and staurosporine-induced apoptosis. Staurosporine, but not the anti-Fas antibody CH11, abrogates constitutive Hsp70 expression at 37 degrees C and staurosporine also inhibit Hsp27 expression in Jd and Jr cells at 42 degrees C. These data suggest that constitutive expression of Hsp27 inhibits Fas-mediated apoptosis, but only induced expression of Hsp70 can protect T cells from staurosporine-induced apoptosis. Thus, Hsp27 could play a role in the regulation of death receptor-mediated apoptosis, while Hsp70 could regulate mitochondrial-dependent cell death.
INSERM U. 526, Activation des Cellules Hématopoiétiques, Equipe Labellisée Ligue Nationale contre le Cancer, IFR50 Faculté de Médecine, avenue de Valombrose, 06107 Nice Cedex 02, France.
J E
JE
Ricci
L
L
Maulon
V
V
Battaglione-Hofman
C
C
Bertolotto
F
F
Luciano
B
B
Mari
P
P
Hofman
P
P
Auberger
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology; D004789:Enzyme Activation; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D019014:fas Receptor / Q000502:physiology
D002518:Ceramides; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D020169:Caspases; D019311:Staurosporine