Cited by 136Cell death mechanisms and regulationMitochondrial Function and PathologyCardiac Ischemia and Reperfusion

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Necrotic Cell Death in Response to Oxidant Stress Involves the Activation of the Apoptogenic Caspase-8/Bid Pathway

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Wang, Xue, Ryter, Stefan W., Dai, Chunsun, Tang, Zi-Lue, Watkins, Simon C., Yin, Xiao-Ming, Song, Ruiping, Choi, Augustine M.K.·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m301624200

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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.

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Authors: Wang, X., Ryter, S. W., Dai, C., Tang, Z.-L., Watkins, S. C., Yin, X.-M., Song, R., & Choi, A. M. K.
Affiliations: University of Pittsburgh (US)
Corresponding author: Choi, Augustine M.K.
ORCID: Wang, Xue
Ryter, Stefan W.
Dai, Chunsun
Watkins, Simon C.
Yin, Xiao-Ming
Choi, Augustine M.K.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-08
Volume: 278
Issue: 31
Pages: 29184-29191
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m301624200
OpenAlex: W2052913152
Cited by: 136
References: 41
Citations by year: 2026: 3 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 2
FWCI: 5.08
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6269 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (7r01ai042365-02)
National Heart, Lung, and Blood Institute (R01HL055330, R01HL55330, R01HL60234, R01HL060234)
National Institute of Allergy and Infectious Diseases (R01 AI-42365)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
Keywords: necrosis, hyperoxia, oxidative stress, caspase-8, Bid, Bax, mitochondrial apoptosis, A549 cells, epithelial cells, hyperoxic lung injury, c-FLIP
MeSH terms: Adenocarcinoma, Animals, Carrier Proteins, Cells, Cultured, Enzyme Inhibitors, Fibroblasts, Humans, Lung, Lung Neoplasms, Male, Membrane Glycoproteins, Mice, Inbred C3H, Mice, Inbred C57BL, Oxygen, Tumor Cells, Cultured, Apoptosis, Gene Deletion, Mice, Knockout, Oxidative Stress, fas Receptor, Caspases, Intracellular Signaling Peptides and Proteins, BH3 Interacting Domain Death Agonist Protein, Mice, Caspase 8, Fas Ligand Protein, CASP8 and FADD-Like Apoptosis Regulating Protein, Caspase 9, Caspase Inhibitors

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Necrotic Cell Death in Response to Oxidant Stress Involves the Activation of the Apoptogenic Caspase-8/Bid Pathway

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