Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes |
| |
Authors: | Bettina Brandt Tom Büchse Ehab Fathi Abou-Eladab Markus Tiedge Eberhard Krause Udo Jeschke Hermann Walzel |
| |
Institution: | Medical Faculty, Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Schillingallee 70, 18057 Rostock, Germany. |
| |
Abstract: | Galectin-1 (gal-1), a member of the family of β-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. |
| |
Keywords: | Galectin-1 T cell apoptosis Death receptor pathway |
本文献已被 PubMed SpringerLink 等数据库收录! |
|