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Galectin-1 Induced Activation of the Mitochondrial Apoptotic Pathway: Evidence for a Connection Between Death-Receptor and Mitochondrial Pathways in Human Jurkat T Lymphocytes

Falko Lange, Bettina Brandt, Markus Tiedge, Ludwig Jonas, Udo Jeschke, Ralf Pöhland, Hermann Walzel

Histochem Cell Biol. 2009 Aug;132(2):211-23.

PMID: 19381674

Abstract:

Galectin-1 (gal-1) triggers T cell death by several distinct intracellular pathways including the activation of the death-receptor pathway. The aim of this study was to investigate whether gal-1 induced activation of the death-receptor pathway in Jurkat T lymphocytes mediates apoptosis via the mitochondrial pathway linked by truncated Bid (tBid). We demonstrate that gal-1 induced proteolytic cleavage of the death agonist Bid, a member of the Bcl-2/Bcl-xL family and a substrate of activated caspase-8, was inhibited by caspase-8 inhibitor II (Z-IETD-FMK). Downstream of Bid, gal-1 stimulated mitochondrial cytochrome c release as well as the activation and proteolytic processing of initiator procaspase-9 were effectively decreased by caspase-8 inhibitor II. Blocking of gal-1 induced cleavage of effector procaspase-3 by caspase-8 inhibitor II as well as by caspase-9 inhibitors I (Z-LEHD-FMK) and III (Ac-LEHD-CMK) indicates that receptor and mitochondrial pathways converged in procaspase-3 activation and contribute to proteolytic processing of effector procaspase-6 and -7. Western blot analyses and immunofluorescence staining revealed that exposure of Jurkat T cells to gal-1 resulted in the cleavage of the DNA-repair enzyme poly (ADP-ribose) polymerase, cytoskeletal alpha-fodrin, and nuclear lamin A as substrates of activated caspases. Our data demonstrate that Bid provides a connection between the death receptor and the mitochondrial pathway of gal-1 induced apoptosis in human Jurkat T lymphocytes.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42415430 Caspase-8 Inhibitor II Caspase-8 Inhibitor II Price
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