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.
Hahn
H P
HP
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Pang
M
M
He
J
J
Hernandez
J D
JD
Yang
R-Y
RY
Li
L Y
LY
Wang
X
X
Liu
F-T
FT
Baum
L G
LG
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