The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Regulation of Hypoxia-Inducible Factor-1a by Reactive Oxygen Species : New Developments in an Old Debate
Abstract
Hypoxia-Inducible Factor-1 (HIF-1) has been largely studied for its role in cell survival in hypoxic conditions. The regulation of HIF-1 is a complex process and involves a number of molecules and pathways. Among these mechanisms a direct regulatory role of reactive oxygen species (ROS) on HIF-1 alpha subunit has received a great deal of attention and the existing body of literature includes many contradictory findings. Other intermediates such as nitric oxide (NO), specific microRNAs (miR), and transcriptional and post-translational modification have also been implicated as players in ROS mediated HIF-1a regulation. The focus of this review is to present the past conflicting evidence along with more recent findings in order to relate various aspects of this complex process. Aside from the direct role of ROS on HIF-1a regulation under hypoxia and normoxia, we analyzed the effect of different sources and concentrations of NO and the interplay between superoxide (SO) and NO in this process. We also present findings on transcriptional and translational regulation of HIF-1a via ROS and the interplay with microRNAs in this process. This review further provides insight on ERK and PI3K/AKT signaling as a common mechanism relating several pathways of ROS mediated HIF-1a regulation. Ultimately further research and discovery regarding HIF-1 regulation by oxidative stress is warranted for better understanding of disease development and potential therapeutics for pathologies such as canc…
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“Therefore, it is plausible that increased levels of 2-HG may enable a switch to an entirely HIF-independent mechanism.”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [160]
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1 retracted
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
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Mitochondrial reactive oxygen species trigger hypoxia-induced transcription
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Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
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Hydroxylation of HIF-1: Oxygen Sensing at the Molecular Level
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Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
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Hypoxia-Inducible mir-210 Regulates Normoxic Gene Expression Involved in Tumor Initiation
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Research works printed but not linked: 2
- Brüne, 2007, Methods in enzymology, 463
- Hagen, 2012, Oxygen versus Reactive Oxygen in the Regulation of HIF-1: The Balance Tips, Biochem Res Int, e436981
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The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy
Muz, B., de la Puente, P., Azab, F., & Azab, A. K. (2015) · Hypoxia · doi:10.2147/hp.s93413 · Cited by 2,066
“42,43 In addition, mitochondrial ROS 44,45 and nitric oxide (NO) 46 were shown to up-or downregulate HIF-1 α accumulation (Figure 1).”
BackgroundROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Davalli, P., Mitic, T., Caporali, A., Lauriola, A., & D’Arca, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3565127 · Cited by 1,059
Heavy metal associated health hazards: An interplay of oxidative stress and signal transduction
Paithankar, J. G., Saini, S., Dwivedi, S., Sharma, A., & Chowdhuri, D. K. (2020) · Chemosphere · doi:10.1016/j.chemosphere.2020.128350 · Cited by 611
The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders
Tarafdar, A., & Pula, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123824 · Cited by 373
Oldham, W. M., Clish, C. B., Yang, Y., & Loscalzo, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.021 · Cited by 364
“…of HIF is complex, and a variety ofmechanisms have been implicated in its stabilization, includingmicroRNA, other post-translationalmodifications, and intracellular signaling cascades (e.g., ERK and AKT), in addition to ROS and PHD inhibition (Movafagh et al., 2015; Yee Koh et al., 2008).”
Metadata
- Authors
- Movafagh, S., Crook, S., & Vo, K.
- Affiliations
- Shenandoah University (US)
- Corresponding author
- Movafagh, Shahrzad
- ORCID
- Movafagh, Shahrzad
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2015-03-09
- Volume
- 116
- Issue
- 5
- Pages
- 696-703
- ISSN
- 0730-2312 (ISSN-L)
- OpenAlex
- W1899746275
- Cited by
- 469
- References
- 50
- Citations by year
- 2026: 23 · 2025: 42 · 2024: 39 · 2023: 56 · 2022: 56 · 2021: 66 · 2020: 54 · 2019: 39 · 2018: 29 · 2017: 31 · 2016: 22 · 2015: 12
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- hypoxia-inducible factor-1α, reactive oxygen species, nitric oxide, superoxide, microRNA, post-translational modification, transcriptional regulation, ERK signaling, PI3K/Akt signaling, oxidative stress, hypoxia, ischemia-reperfusion injury, cancer
- MeSH terms
- Humans, Mitochondria, Nitric Oxide, Superoxides, Signal Transduction, Cell Hypoxia, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, MicroRNAs, Proto-Oncogene Proteins c-akt, Hypoxia-Inducible Factor 1, alpha Subunit
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