Caspase-dependent inhibition of store-operated Ca(2+) entry into apoptosis-committed Jurkat cells.
Activation of T-cells triggers store-operated Ca(2+) entry, which begins a signaling cascade leading to induction of appropriate gene expression and eventually lymphocyte proliferation and differentiation. The simultaneous enhancement of Fas ligand gene expression in activated cells allows the immune response to be limited by committing the activated cells to apoptosis. In apoptotic cells the store-operated calcium entry is significantly inhibited. It has been documented that moderate activation of Fas receptor may cause reversible inhibition of store-operated channels by ceramide released from hydrolyzed sphingomyelin. Here we show that activation of Fas receptor in T-cells results in caspase-dependent decrease of cellular STIM1 and Orai1 protein content. This effect may be responsible for the substantial inhibition of Ca(2+) entry into Jurkat cells undergoing apoptosis. In turn, this inhibition might prevent overloading of cells with calcium and protect them against necrosis.
Onopiuk
Marta
M
Department of Biochemistry, The Nencki Institute of Experimental Biology, Warsaw, Poland.
Wierzbicka
Katarzyna
K
Brutkowski
Wojciech
W
Szczepanowska
Joanna
J
Zabłocki
Krzysztof
K
D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019014:fas Receptor / Q000819:agonists / Q000378:metabolism
D000906:Antibodies; C481004:CH-11 anti-fas antibody, human; D015220:Calcium Channels; D061945:Caspase Inhibitors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D019014:fas Receptor; D020169:Caspases; D002118:Calcium