Characterization of galectin-9-induced death of Jurkat T cells.
Galectin-9, a mammalian lectin with affinity for beta-galactosides, is known as an apoptosis inducer of activated T lymphocytes. In the present study, we examined the properties of galectin-9-mediated cell death of Jurkat T cells. Galectin-9NC (wild-type), consisting of two CRDs (N-terminal and C-terminal carbohydrate recognition domains), and derivatives of it, galectins-9-NN and -9-CC, induced Jurkat T-cell apoptosis. However, a single CRD (galectin-9NT or -CT) had no effect, suggesting the stable dimeric structure of two CRDs is required for the activity. The apoptosis was inhibited by pretreatment with an N-glycan synthesis inhibitor, indicating that the expression of N-glycans in the cells is essential for galectin-9-induced apoptosis. We previously showed that the apoptosis of MOLT-4 cell is mediated by galectin-9 via a Ca(2+)-calpain-caspase-1-dependent pathway. In Jurkat cells, the cell death by galectin-9, was insufficiently suppressed by caspase inhibitors, Ca(2+)-chelator or calpain inhibitor. Furthermore, we observed the loss of mitochondrial membrane potential and significant AIF release in galectin-9-treated cells. These findings suggest that caspase-dependent and-independent death pathways exist in Jurkat cells, and the main pathway might vary with the T-cell type.
Lu
Liang-Hao
LH
Department of Endocrinology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Nakagawa
Ryusuke
R
Kashio
Yumiko
Y
Ito
Aiko
A
Shoji
Hiroki
H
Nishi
Nozomu
N
Hirashima
Mitsuomi
M
Yamauchi
Akira
A
Nakamura
Takanori
T
D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*
D015853:Cysteine Proteinase Inhibitors; D037161:Galectins; C105032:LGALS9 protein, human; D011994:Recombinant Proteins; D020170:Caspase 1; D002118:Calcium