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Galectin-1 Induced Activation of the Apoptotic Death-Receptor Pathway in Human Jurkat T Lymphocytes

Bettina Brandt, Tom Büchse, Ehab Fathi Abou-Eladab, Markus Tiedge, Eberhard Krause, Udo Jeschke, Hermann Walzel

Histochem Cell Biol. 2008 May;129(5):599-609.

PMID: 18288482

Abstract:

Galectin-1 (gal-1), a member of the family of beta-galactoside binding proteins, participates in several biological processes such as immunomodulation, cell adhesion, regulation of cell growth and apoptosis. The aim of this study was to investigate whether gal-1 interferes with the Fas (Apo-1/CD95)-associated apoptosis cascade in the T-cell lines Jurkat and MOLT-4. Gal-1 and an Apo-1 monoclonal antibody (mAb) induced DNA-fragmentation in Jurkat T-cells whereas MOLT-4 cells were resistant. Gal-1 stimulated DNA-fragmentation could be efficiently inhibited by caspase-8 inhibitor II (Z-IETD-FMK) and a neutralizing Fas mAb. Fas could be identified as a target for gal-1 recognition as demonstrated by immunofluorescence staining, binding of the receptor glycoprotein to immobilized gal-1 and analyses by immunoblotting as well as by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gal-1 stimulates the activation and proteolytic processing of procaspase-8 and downstream procaspase-3 in Jurkat-T cells. Inhibition of gal-1 induced procaspase-8 activation by a neutralizing Fas mAb strongly suggests that gal-1 recognition of Fas is associated with caspase-8 activation. Our data provide the first experimental evidence for targeting of gal-1 to glycotopes on Fas and the subsequent activation of the apoptotic death-receptor pathway.

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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