Sustained release of Smac/DIABLO from mitochondria commits to undergo UVB-induced apoptosis.
Apoptotic response of keratinocytes to UVB irradiation has physiological significance on photocarcinogenesis. Here, we show that the sustained release of Smac/DIABLO from mitochondria is an important event for the onset of apoptosis in keratinocytes exposed to UVB irradiation. In human keratinocyte HaCaT cells, UVB irradiation at 500 J/m(2), but not at 150 J/m(2), induces apoptosis. Significant activations of caspases-9 and -3, and slight activation of caspase-7 were observed only in 500 J/m(2) UVB irradiated HaCaT cells. Correspondingly, the cleavage of PARP, a substrate of caspases-3 and -7, was detected in cells irradiated at 500 J/m(2) UVB, but not at 150 J/m(2). However, with both 150 and 500 J/m(2) UVB irradiation, cytochrome c, an activator of caspase-9 via the formation of apoptosome, was released from mitochondria to the cytosol at the same extent. In contrast, significant amounts of Smac/DIABLO are released from mitochondria to the cytosol only with 500 J/m(2) UVB irradiation, and that the level of XIAP is decreased. These results suggest that the extent of Smac/DIABLO efflux from mitochondria is a determinant whether a cell will undergo apoptosis or survival.
Takasawa
R
R
Genome & Drug Research Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-0022, Japan.
Tanuma
S
S
D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism* / Q000528:radiation effects*; D020169:Caspases / Q000378:metabolism / Q000528:radiation effects; D002461:Cell Line, Transformed; D045304:Cytochromes c / Q000378:metabolism / Q000528:radiation effects; D003600:Cytosol / Q000378:metabolism / Q000528:radiation effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects*; D024101:Mitochondrial Proteins / Q000378:metabolism* / Q000528:radiation effects*; D021381:Protein Transport / Q000502:physiology / Q000528:radiation effects; D011506:Proteins / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D051636:X-Linked Inhibitor of Apoptosis Protein
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D045304:Cytochromes c; D020169:Caspases