Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801 , Involved in Apoptosis
Open accessAbstract
Hypoxia is an important factor that elicits numerous physiological and pathological responses. One of the major gene expression programs triggered by hypoxia is mediated through hypoxia-responsive transcription factor hypoxia-inducible factor 1 (HIF-1). Here, we report the identification and cloning of a novel HIF-1-responsive gene, designated RTP801. Its strong up-regulation by hypoxia was detected both in vitro and in vivo in an animal model of ischemic stroke. When induced from a tetracycline-repressible promoter, RTP801 protected MCF7 and PC12 cells from hypoxia in glucose-free medium and from H(2)O(2)-triggered apoptosis via a dramatic reduction in the generation of reactive oxygen species. However, expression of RTP801 appeared toxic for nondividing neuron-like PC12 cells and increased their sensitivity to ischemic injury and oxidative stress. Liposomal delivery of RTP801 cDNA to mouse lungs also resulted in massive cell death. Thus, the biological effect of RTP801 overexpression depends on the cell context and may be either protecting or detrimental for cells under conditions of oxidative or ischemic stresses. Altogether, the data suggest a complex type of involvement of RTP801 in the pathogenesis of ischemic diseases.
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- Authors
- Shoshani, T., Faerman, A., Mett, I., Zelin, E., Tenne, T., Gorodin, S., Moshel, Y., Elbaz, S., Budanov, A., Chajut, A., Kalinski, H., Kamer, I., Rozen, A., Mor, O., Keshet, E., Leshkowitz, D., Einat, P., Skaliter, R., & Feinstein, E.
- Affiliations
- Quark Biotech
- University of Illinois Chicago (US)
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Feinstein, Elena
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2002-04
- Volume
- 22
- Issue
- 7
- Pages
- 2283-2293
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC133671
- OpenAlex
- W2101208037
- Cited by
- 546
- References
- 5
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 14 · 2023: 14 · 2022: 25 · 2021: 42 · 2020: 14 · 2019: 21 · 2018: 22 · 2017: 15 · 2016: 27 · 2015: 17 · 2014: 41 · 2013: 22 · 2012: 27
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- RTP801, HIF-1, hypoxia, apoptosis, ischemic stroke, oxidative stress, reactive oxygen species, ischemic injury, liposomal gene delivery, neuroprotection
- MeSH terms
- Amino Acid Sequence, Animals, Hypoxia, Base Sequence, Cell Differentiation, Cloning, Molecular, DNA-Binding Proteins, Gene Expression Regulation, Humans, Hydrogen Peroxide, Liposomes, Lung, Molecular Sequence Data, Nuclear Proteins, Repressor Proteins, RNA, Messenger, Transcription Factors, Tumor Cells, Cultured, Up-Regulation, PC12 Cells, Apoptosis, Reactive Oxygen Species, Sequence Homology, Amino Acid, In Situ Hybridization, Stroke, Adaptor Proteins, Signal Transducing, Mice, Rats, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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