Journal article
An early oxygen-dependent step is required for dexamethasone-induced apoptosis of immature mouse thymocytes
The Journal of immunology (1950), v 165(9), pp 4822-4830
01 Nov 2000
PMID: 11046005
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The roles of oxygen and reactive oxygen intermediates in apoptosis are unclear at present. Although oxygen and reactive oxygen intermediates are not required for the execution of apoptosis, oxygen may be involved in at least some forms of apoptosis, In this study we show that dexamethasone (Dex)-induced apoptosis of immature mouse thymocytes is completely inhibited by hypoxic culture. In contrast, anti-CD95 thymocyte apoptosis is unaffected by hypoxia, indicating the existence of two forms of thymocyte apoptosis: an oxygen-dependent pathway (Des induced) and an oxygen-independent pathway (anti-CD95 induced). Furthermore, hypoxia inhibited mitochondrial permeability transition CPT in Des-treated, but not in anti-CD95-treated, thymocytes, suggesting that the oxygen-sensitive step is upstream of mitochondria, Both Dex- and anti-CD95-induced PT and apoptosis were dependent on activation of Ii-converting enzyme-like protease, as PT and apoptosis were inhibited by preincubation with Cbz-Val-Ala-Asp-fluoromethyl ketone, an irreversible inhibitor of IL-converting enzyme-like proteases, In addition, hypoxia inhibited the activation by Dex of caspase-3 (CPP32)-like proteases, Our data show that the private signaling pathways of Dex (oxygen dependent) and anti-CD95 (oxygen independent) both converge upstream of mitochondrial changes. The oxygen-dependent step in Dex-induced apoptosis lies upstream of caspase-3-like protease activation, Our observations support a model of apoptosis signaling in which independent pathways (oxygen dependent and oxygen independent) particular to each stimuli converge at a central point in the apoptotic cascade.
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Details
- Title
- An early oxygen-dependent step is required for dexamethasone-induced apoptosis of immature mouse thymocytes
- Creators
- J F Torres-Roca - Stanford UniversityJ W Tung - Departments of Genetics andD R Greenwald - Departments of Genetics andJ M Brown - Stanford UniversityL A Herzenberg - Departments of Genetics andL A Herzenberg - Departments of Genetics andP D Katsikis - Drexel University
- Publication Details
- The Journal of immunology (1950), v 165(9), pp 4822-4830
- Publisher
- American Association of Immunologists
- Number of pages
- 9
- Grant note
- R01AI031770 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R35CA042509 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CA42509 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01LM004836 / NATIONAL LIBRARY OF MEDICINE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM) LM04836 , + / NLM NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM) AI31770 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physical Therapy (and Rehabilitation Sciences)
- Web of Science ID
- WOS:000090076000009
- Scopus ID
- 2-s2.0-0034327754
- Other Identifier
- 991019168265304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology