Effects of N-glycan processing inhibitors on signaling events and induction of apoptosis in galectin-1-stimulated Jurkat T lymphocytes.
To elucidate the role of N-linked glycans in triggering T-cell functions, the effects of the N-glycan processing inhibitors 1-deoxymannojirimycin (1-DMM) and swainsonine (SW) were investigated on signaling events and induction of apoptosis in galectin-1 (gal-1)-stimulated Jurkat T lymphocytes. The treatment of Jurkat E6.1 cells with 1-DMM and SW strongly reduced the cell binding of gal-1-biotin, conjugate binding to cell lysate glycoproteins, and to cluster of differentiation (CD) 3 immunoprecipitates on blots as well as the binding of CD2 and CD3 to immobilized gal-1. The mannosidase inhibitors efficiently decreased gal-1-induced calcium mobilization. Both phases originated from a transient Ca(2+) release of internal stores, and the sustained influx across the plasma membrane was found to be involved. Both inhibitors suppressed in transiently transfected Jurkat T lymphocytes the gal-1-induced expression of the luciferase (luc) reporter gene constructs pNFAT-TA-Luc and pAP1(phorbol-12-myristate-13-acetate [PMA])-TA-Luc. The data provide evidence that gal-1 triggers through binding to N-linked glycans a Ca(2+)-sensitive apoptotic pathway.
Walzel
Hermann
H
Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Schillingallee 70, D-18057 Rostock, Germany. hermann.walzel@med.uni-rostock.de
Fahmi
Abdelgawad A
AA
Eldesouky
Mohamed A
MA
Abou-Eladab
Ehab F
EF
Waitz
Grit
G
Brock
Josef
J
Tiedge
Markus
M
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D000073718:Pancreatitis-Associated Proteins; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D015398:Signal Transduction; D017026:Swainsonine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*
D004791:Enzyme Inhibitors; D037483:Galectin 1; D000073718:Pancreatitis-Associated Proteins; D010835:Phytohemagglutinins; D011134:Polysaccharides; C000612141:REG3A protein, human; D017485:1-Deoxynojirimycin; D008156:Luciferases; D017026:Swainsonine; D002118:Calcium