Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death.
Galectin-1, a mammalian lectin expressed in many tissues, induces death of diverse cell types, including lymphocytes and tumor cells. The galectin-1 T cell death pathway is novel and distinct from other death pathways, including those initiated by Fas and corticosteroids. We have found that galectin-1 binding to human T cell lines triggered rapid translocation of endonuclease G from mitochondria to nuclei. However, endonuclease G nuclear translocation occurred without cytochrome c release from mitochondria, without nuclear translocation of apoptosis-inducing factor, and prior to loss of mitochondrial membrane potential. Galectin-1 treatment did not result in caspase activation, nor was death blocked by caspase inhibitors. However, galectin-1 cell death was inhibited by intracellular expression of galectin-3, and galectin-3 expression inhibited the eventual loss of mitochondrial membrane potential. Galectin-1-induced cell death proceeds via a caspase-independent pathway that involves a unique pattern of mitochondrial events, and different galectin family members can coordinately regulate susceptibility to cell death.
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA.
H P
HP
Hahn
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M
Pang
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J
He
J D
JD
Hernandez
R-Y
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Yang
L Y
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Li
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Wang
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FT
Liu
L G
LG
Baum
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005420:Flavoproteins / Q000378:metabolism; D037483:Galectin 1 / Q000378:metabolism / Q000502:physiology*; D037502:Galectin 3 / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D019169:Jurkat Cells; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005420:Flavoproteins; D037483:Galectin 1; D037502:Galectin 3; D008565:Membrane Proteins; D045304:Cytochromes c; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases