Cited by 469Cancer, Hypoxia, and MetabolismRedox biology and oxidative stressNitric Oxide and Endothelin Effects

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Regulation of Hypoxia-Inducible Factor-1a by Reactive Oxygen Species : New Developments in an Old Debate

Movafagh, Shahrzad, Crook, Sean, Vo, Kim·2015·Journal of Cellular Biochemistry

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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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Retracted
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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)
DOI: 10.1002/jcb.25074
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
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 176 d)
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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Regulation of Hypoxia-Inducible Factor-1a by Reactive Oxygen Species : New Developments in an Old Debate

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