ArticleJournal of molecular medicine (Berlin, Germany)2016
Differential transcriptional regulation of hypoxia-inducible factor-1α by arsenite under normoxia and hypoxia: involvement of Nrf2.
Article in Journal of molecular medicine (Berlin, Germany), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- RPLP2 activates TLR4 in an autocrine manner and promotes HIF-1α-induced metabolic reprogramming in hepatocellular carcinoma.Cell death discovery · 2023Article
- An antioxidant response element regulates the HIF1α axis in breast cancer cells.Free radical biology & medicine · 2023Article
- The role of hypoxia-inducible factor 1 alpha (HIF-1α) modulation in heavy metal toxicity.Archives of toxicology · 2023Review
- NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy.Cell death & disease · 2022Article
- Vitamin D and Hypoxia: Points of Interplay in Cancer.Cancers · 2022Review
- Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape.Free radical biology & medicine · 2021Article
- Emerging Roles of N6-Methyladenosine (m6A) Epitranscriptomics in Toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- UBXN7 cofactor of CRL3Biochimica et biophysica acta. Molecular cell research · 2021Article
- hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway.Frontiers in oncology · 2021Article
- The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity.International journal of molecular sciences · 2020Review
- Induction of Redox-Active Gene Expression by CoClAntioxidants (Basel, Switzerland) · 2019Article
- Liver Zonation in Health and Disease: Hypoxia and Hypoxia-Inducible Transcription Factors as Concert Masters.International journal of molecular sciences · 2019Review
- Review
- Identification of a functional antioxidant response element at the HIF1A locus.Redox biology · 2018Article
- Non-electron transfer chain mitochondrial defects differently regulate HIF-1α degradation and transcription.Redox biology · 2017Article
- The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system.British journal of pharmacology · 2017Review
- Metabolic zonation of the liver: The oxygen gradient revisited.Redox biology · 2017Review
- Long-Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF-7 Cells.Oxidative medicine and cellular longevity · 2016Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arsenite (As(III)) is widely distributed in nature and can be found in water, food, and air. There is significant evidence that exposure to As(III) is associated with human cancers originated from liver, lung, skin, bladder, kidney, and prostate. Hypoxia plays a role in tumor growth and aggressiveness; adaptation to it is, at least to a large extent, mediated by hypoxia-inducible factor-1α (HIF-1α). In the current study, we investigated As(III) effects on HIF-1α under normoxia and hypoxia in the hepatoma cell line HepG2. We found that As(III) increased HIF-1α protein levels under normoxia while the hypoxia-mediated induction of HIF1α was reduced. Thereby, the As(III) effects on HIF-1α were dependent on both, transcriptional regulation via the transcription factor Nrf2 mediated by NOX4, PI3K/Akt, and ERK1/2 as well as by modulation of HIF-1α protein stability. In line, the different effects of As(III) via participation of HIF-1α and Nrf2 were also seen in tube formation assays with endothelial cells where knockdown of Nrf2 and HIF-1α abolished As(III) effects. Overall, the present study shows that As(III) is a potent inducer of HIF-1α under normoxia but not under hypoxia which may explain, in part, its carcinogenic as well as anti-carcinogenic actions. KEY MESSAGE: As(III) increased HIF-1α under normoxia but reduced its hypoxia-dependent induction. The As(III) effects on HIF-1α were dependent on ROS, NOX4, PI3K/Akt, and ERK1/2. The As(III) effects under normoxia involved transcriptional regulation via Nrf2. Knockdown of Nrf2 and HIF-1α abolished As(III) effects in tube formation assays. The data may partially explain As(III)'s carcinogenic and anti-carcinogenic actions.
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