ArticlePloS one2013
Insulin regulates hypoxia-inducible factor-1α transcription by reactive oxygen species sensitive activation of Sp1 in 3T3-L1 preadipocyte.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- N-acetylcysteine restores osteogenesis in human periodontal ligament stem cells by attenuating HIF-1α-driven oxidative stress and glycolytic reprogramming.Journal of dental sciences · 2026Article
- Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer.Cellular & molecular biology letters · 2025Review
- Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development.Current issues in molecular biology · 2023Review
- Hypoxia‑inducible factors in hepatocellular carcinoma (Review).Oncology reports · 2020Review
- Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction.Biomolecules · 2018Review
- The role of hypoxic signalling in metastasis: towards translating knowledge of basic biology into novel anti-tumour strategies.Clinical & experimental metastasis · 2018Review
- SINHCAF/FAM60A and SIN3A specifically repress HIF-2α expression.The Biochemical journal · 2018Article
- The effect of within-instar development on tracheal diameter and hypoxia-inducible factors α and β in the tobacco hornworm, Manduca sexta.Journal of insect physiology · 2018Article
- Hypoxia in Obesity and Diabetes: Potential Therapeutic Effects of Hyperoxia and Nitrate.Oxidative medicine and cellular longevity · 2017Review
- Left-Biased Spermatogenic Failure in 129/SvJ Dnd1Ter/+ Mice Correlates with Differences in Vascular Architecture, Oxygen Availability, and Metabolites.Biology of reproduction · 2015Article
- Molecular mechanisms of action and therapeutic uses of pharmacological inhibitors of HIF-prolyl 4-hydroxylases for treatment of ischemic diseases.Antioxidants & redox signaling · 2014Review
- Transcriptional repression of hypoxia-inducible factor-1 (HIF-1) by the protein arginine methyltransferase PRMT1.Molecular biology of the cell · 2014Article
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Authors and funding
5 authors.
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Abstract
Oxygen sensing transcription factor HIF-1 is activated due to accumulation of regulatory subunit HIF-1α by posttranslational stability mechanism during hypoxia or by several other stimuli even in normoxia. HIF-1α is also regulated by NF-kB mediated transcription mechanism. Reactive oxygen species (ROS) act as an important regulator of HIF-1 either by affecting prolyl hydroxylase activity, the critical determinant of HIF-1α stabilization or by activating NF-kB to promote HIF-1α transcription. Insulin is known to activate HIF-1 by a ROS dependent mechanism but the molecular mechanism of HIF-1α regulation is not known so far. Here we show that insulin regulates HIF-1α by a novel transcriptional mechanism by a ROS-sensitive activation of Sp1 in 3T3-L1 preadipocyte. Insulin shows little effect on HIF-1α protein stability, but increases HIF-1α promoter activity. Mutation analyses, electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirm the role of Sp1 in HIF-1α transcription. We further demonstrate that insulin-induced ROS generation initiates signaling pathway involving phosphatidylinositol 3-kinase and protein kinase C for Sp1 mediated HIF-1α transcription. In summary, we reveal that insulin regulates HIF-1α by a novel transcriptional mechanism involving Sp1.
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