Necrotic cell death in response to oxidant stress involves the activation of the apoptogenic caspase-8/bid pathway

Xue Wang, Stefan W. Ryter, Chunsun Dai, Zi Lue Tang, Simon C. Watkins, Xiao-Ming Yin, Ruiping Song, Augustine M K Choi

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Human epithelial (A549) cells exposed to hyperoxia die by cellular necrosis. In the current study, we demonstrated the involvement of apoptogenic factors in epithelial cell necrosis in response to hyperoxia, including the formation of the Fas-related death-inducing signaling complex and initiation of mitochondria-dependent apoptotic pathways. We showed increased activation of both Bid and Bax in A549 cells subjected to hyperoxia. Bax activation involved a Bid-assisted conformational change. We discovered that the response to hyperoxia in vivo predominantly involved the activation of the Bid/caspase-8 pathway without apparent increases in Bax expression. Disruption of the Bid pathway by gene deletion protected against cell death in vivo and in vitro. Likewise, inhibition of caspase-8 by Flip also protected against cell death. Taken together, we have demonstrated the involvement of apoptogenic factors in epithelial cell responses to hyperoxia, despite a final outcome of cellular necrosis. We have, for the first time, identified a predominant role for the caspase-8/Bid pathway in signaling associated with hyperoxic lung injury and cell death in vivo and in vitro.

Original languageEnglish (US)
Pages (from-to)29184-29191
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number31
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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Hyperoxia
Caspase 8
Cell death
Oxidants
Cell Death
Chemical activation
Death Domain Receptor Signaling Adaptor Proteins
Necrosis
Epithelial Cells
Mitochondria
Genes
Gene Deletion
Lung Injury

ASJC Scopus subject areas

  • Biochemistry

Cite this

Necrotic cell death in response to oxidant stress involves the activation of the apoptogenic caspase-8/bid pathway. / Wang, Xue; Ryter, Stefan W.; Dai, Chunsun; Tang, Zi Lue; Watkins, Simon C.; Yin, Xiao-Ming; Song, Ruiping; Choi, Augustine M K.

In: Journal of Biological Chemistry, Vol. 278, No. 31, 01.08.2003, p. 29184-29191.

Research output: Contribution to journalArticle

Wang, Xue ; Ryter, Stefan W. ; Dai, Chunsun ; Tang, Zi Lue ; Watkins, Simon C. ; Yin, Xiao-Ming ; Song, Ruiping ; Choi, Augustine M K. / Necrotic cell death in response to oxidant stress involves the activation of the apoptogenic caspase-8/bid pathway. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 31. pp. 29184-29191.
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AU - Watkins, Simon C.

AU - Yin, Xiao-Ming

AU - Song, Ruiping

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