Differential activation of phospholipases during necrosis or apoptosis: a comparative study using tumor necrosis factor and anti-Fas antibodies.
Phospholipases generate important secondary messengers in several cellular processes, including cell death. Tumor necrosis factor (TNF) can induce two distinct modes of cell death, viz. necrosis and apoptosis. Here we demonstrate that phospholipase D (PLD) and cytosolic phospholipase A2 (cPLA2) are differentially activated during TNF-induced necrosis or apoptosis. Moreover, a comparative study using TNF and anti-Fas antibodies as cell death stimuli showed that PLD and cPLA2 are specifically activated by TNF. These results indicate that both the mode of cell death and the type of death stimulus determine the potential role of phospholipases as generators of secondary messengers.
De Valck
D
D
Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Gent, Belgium.
Vercammen
D
D
Fiers
W
W
Beyaert
R
R
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D020404:Glycerophospholipids / Q000378:metabolism; D006801:Humans; D051379:Mice; D009336:Necrosis; D010739:Phospholipase D / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010766:Phosphorylation / Q000187:drug effects; D011003:Ploidies; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000276:immunology* / Q000502:physiology
D000906:Antibodies; D020404:Glycerophospholipids; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C051521:phosphatidylethanol; D016718:Arachidonic Acid; D000001:Calcimycin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate