期刊
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
卷 20, 期 12, 页码 1121-1129出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/107999000750053799
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Interferon-alpha (IFN-alpha) displays antitumor action by inducing direct cytotoxicity against tumor cells in addition to generation of cytotoxic cells. The IFN-alpha -induced direct cytotoxicity is at least partly due to induction of apoptosis, In the present study, we examined signaling pathways implicated in IFN-alpha -induced apoptosis in Daudi cells. Release of cytochrome c from mitochondria to cytosol was found after 12 h incubation with IFN-alpha, followed by a decline in mitochondrial membrane potential (Delta psi (m)) and procaspase-3 activation at 24 and 36 h, respectively. Cleavage of endogenous Bax-alpha (21 kDa), generating an 18-kDa fragment (p18 Bax-alpha), was found at 36 h. Although the endogenous p21 Bax-alpha was located in both cytosol and mitochondrial membranes, the p18 Bax-alpha resided only on mitochondrial membranes. IFN-alpha -induced apoptosis occurred 48 h after stimulation, with a further increase in proportion up to 72 h. Pretreatment with pancaspase inhibitor Z-VAD-fmk substantially inhibited the IFN-alpha -mediated Bax-alpha cleavage and apoptosis, but not the decline in Delta psi (m), suggesting the possibility that caspase-3 activation is implicated in the Bax-alpha cleavage, probably leading to amplification of the apoptotic processes. Our results suggest that modulation of endogenous p21 Bax-alpha is implicated in IFN-alpha -induced apoptosis.
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