ArticlePloS one2015
HIF-1α activation by intermittent hypoxia requires NADPH oxidase stimulation by xanthine oxidase.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 91 citations in OpenAlex.
- Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea.Experimental physiology · 2018Trial
- Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression.Experimental biology and medicine (Maywood, N.J.) · 2017Trial
- Lung Vascular Remodeling and Oxidative Damage Induced by Chronic Intermittent Hypoxia.International journal of molecular sciences · 2026Article
- Intermittent hypoxia aggravates asthma inflammation via NLRP3/IL-1β-dependent pyroptosis mediated by HIF-1α signalling pathway.Chinese medical journal · 2025Article
- In defence of ferroptosis.Signal transduction and targeted therapy · 2025Review
- Febuxostat therapy improved the outcomes of cardiorenal syndrome rodent through alleviating xanthine oxidase-induced oxidative stress and mitochondrial dysfunction.International journal of biological sciences · 2025Article
- Relationship between cognitive dysfunction and urinary 8-OHdG levels in children with obstructive sleep apnea.Frontiers in neurology · 2025Article
- Molecular and Clinical Perspectives on the Regulation of Sleep and Uric Acid Metabolism.Nature and science of sleep · 2025Review
- Role of HIF1A gene polymorphisms with serum uric acid and HIF-1α levels in monosodium urate crystal-induced arthritis.Clinical rheumatology · 2024Article
- Role of Oxidative Stress in the Occurrence and Development of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea Syndrome.Molecular neurobiology · 2024Review
- Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species.International journal of molecular sciences · 2024Review
- Intermittent hypoxia induces hepatic senescence through promoting oxidative stress in a mouse model.Sleep & breathing = Schlaf & Atmung · 2024Article
- Possible Molecular Mechanisms of Hypertension Induced by Sleep Apnea Syndrome/Intermittent Hypoxia.Life (Basel, Switzerland) · 2024Review
- Expression of Concern: HIF-1α Activation by Intermittent Hypoxia Requires NADPH Oxidase Stimulation by Xanthine Oxidase.PloS one · 2024Article
- Pharmacological modulation of HIF-1 in the treatment of neuropsychiatric disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- How Nitric Oxide Hindered the Search for Hemoglobin-Based Oxygen Carriers as Human Blood Substitutes.International journal of molecular sciences · 2023Review
- Infectious Risk and Variability of Hemoglobin Level in Patients Undergoing Hemodialysis.Kidney international reports · 2023Article
- Protein phosphatase 1 regulates reactive oxygen species-dependent degradation of histone deacetylase 5 by intermittent hypoxia.American journal of physiology. Cell physiology · 2022Article
- The double faced role of xanthine oxidoreductase in cancer.Acta pharmacologica Sinica · 2022Review
- Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway.Chinese journal of integrative medicine · 2022Article
Corrections and comments
- Expression of concern · 2024-02-14Concerns/Issues about Image · Investigation by Journal/Publisher · Original Data and/or Images not Provided and/or not Available ·
- Expression of concern
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factor 1 (HIF-1) mediates many of the systemic and cellular responses to intermittent hypoxia (IH), which is an experimental model that simulates O2 saturation profiles occurring with recurrent apnea. IH-evoked HIF-1α synthesis and stability are due to increased reactive oxygen species (ROS) generated by NADPH oxidases, especially Nox2. However, the mechanisms by which IH activates Nox2 are not known. We recently reported that IH activates xanthine oxidase (XO) and the resulting increase in ROS elevates intracellular calcium levels. Since Nox2 activation requires increased intracellular calcium levels, we hypothesized XO-mediated calcium signaling contributes to Nox activation by IH. We tested this possibility in rat pheochromocytoma PC12 cells subjected to IH consisting alternating cycles of hypoxia (1.5% O2 for 30 sec) and normoxia (21% O2 for 5 min). Kinetic analysis revealed that IH-induced XO preceded Nox activation. Inhibition of XO activity either by allopurinol or by siRNA prevented IH-induced Nox activation, translocation of the cytosolic subunits p47phox and p67phox to the plasma membrane and their interaction with gp91phox. ROS generated by XO also contribute to IH-evoked Nox activation via calcium-dependent protein kinase C stimulation. More importantly, silencing XO blocked IH-induced upregulation of HIF-1α demonstrating that HIF-1α activation by IH requires Nox2 activation by XO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.