期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 281, 期 9, 页码 5837-5844出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M511562200
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Bcl- 2 homology domain ( BH) 3- only proteins couple stress signals to evolutionarily conserved mitochondrial apoptotic pathways. Caspase 8- mediated cleavage of the BH3- only protein Bid into a truncated protein ( tBid) and subsequent translocation of tBid to mitochondria has been implicated in death receptor signaling. We utilized a recombinant fluorescence resonance energy transfer ( FRET) Bid probe to determine the kinetics of Bid cleavage and tBid translocation during death receptor- induced apoptosis in caspase 3- deficient MCF- 7 cells. Cells treated with tumor necrosis factor-alpha ( 200 ng/ ml) showed a rapid cleavage of the Bid- FRET probe occurring 75.4 +/- 12.6 min after onset of the tumor necrosis factor-alpha exposure. Cleavage of the Bid- FRET probe coincided with a translocation of tBid to the mitochondria and a collapse of the mitochondrial membrane potential ( Delta Psi m). We next investigated the role of Bid cleavage in a model of caspase- independent, glutamate- induced excitotoxic apoptosis. Rat cerebellar granule neurons were transfected with the Bid- FRET probe and exposed to glutamate for 5 min. In contrast to death receptor- induced apoptosis, neurons showed a translocation of full- length Bid to the mitochondria. This translocation occurred 5.6 +/- 1.7 h after the termination of the glutamate exposure and was also paralleled with a collapse of the Delta Psi m. Proteolytic cleavage of the FRET probe also occurred, however, only 25.2 +/- 3.5 min after its translocation to the mitochondria. Subfractionation experiments confirmed a translocation of full- length Bid from the cytosolic to the mitochondrial fraction during excitotoxic apoptosis. Our data demonstrate that both tBid and full- length Bid have the capacity to translocate to mitochondria during apoptosis.
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