ArticleAmerican journal of physiology. Cell physiology2011
Transcriptional regulation of the Menkes copper ATPase (Atp7a) gene by hypoxia-inducible factor (HIF2{alpha}) in intestinal epithelial cells.
Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- Skeletal muscle-specific Bambi deletion induces hypertrophy and oxidative switching coupling with adipocyte thermogenesis against metabolic disorders.Science China. Life sciences · 2025Article
- Altered copper transport in oxidative stress-dependent brain endothelial barrier dysfunction associated with Alzheimer's disease.Vascular pharmacology · 2024Article
- Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development.Metallomics : integrated biometal science · 2024Review
- Article
- Co-Administration of Roxadustat and Zinc Stabilizes Both Serum Copper and Zinc Concentrations in Patients Undergoing Hemodialysis.Nutrients · 2023Article
- Whole-Transcriptome Analysis of Yak and Cattle Heart Tissues Reveals Regulatory Pathways Associated With High-Altitude Adaptation.Frontiers in genetics · 2021Article
- Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets.Nutrients · 2020Article
- Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver.Comprehensive Physiology · 2018Review
- Transient HIF2A inhibition promotes satellite cell proliferation and muscle regeneration.The Journal of clinical investigation · 2018Article
- 8-Hydroxyquinolines Are Boosting Agents of Copper-Related Toxicity in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2016Article
- Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells.Metallomics : integrated biometal science · 2016Article
- ROS and intracellular ion channels.Cell calcium · 2016Review
- High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats.PloS one · 2016Article
- Metal-Dependent Regulation of ATP7A and ATP7B in Fibroblast Cultures.Frontiers in molecular neuroscience · 2016Article
- Duodenal cytochrome b (DCYTB) in iron metabolism: an update on function and regulation.Nutrients · 2015Review
- Mechanistic and regulatory aspects of intestinal iron absorption.American journal of physiology. Gastrointestinal and liver physiology · 2014Review
- Molecular mediators governing iron-copper interactions.Annual review of nutrition · 2014Review
- Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Iron homeostasis-related genes (e.g., Dmt1 and Dcytb) are upregulated by hypoxia-inducible factor 2α (HIF2α) during iron deficiency in the mammalian intestine. Menkes copper ATPase (Atp7a) gene expression is also strongly induced in the duodenum of iron-deficient rats. The current study was thus designed to test the hypothesis that Atp7a is regulated by HIF2α. Rat intestinal epithelial (IEC-6) cells were utilized to model the intestinal epithelium, and CoCl(2) and 1% O(2) were applied to mimic hypoxia in vitro. Both treatments significantly increased endogenous Atp7a mRNA levels; mRNA induction with CoCl(2) treatment was blunted by a transcriptional inhibitor. The rat Atp7a promoter was thus cloned and studied. Various sized promoter constructs were inserted into a luciferase reporter vector and transfected into cells. A -224/+88 bp construct had full activity and was induced by CoCl(2); this promoter fragment was thus utilized for subsequent analyses. Interestingly, this region contains three phylogenetically conserved, putative hypoxia response elements (HRE; 5'-NCGTGN-3'). It was further noted that HIF2α overexpression caused a significant upregulation of promoter activity while HIF1α overexpression had little effect. To determine whether Atp7a is a direct HIF target, three putative HREs were deleted individually or in combination; all were shown to be essential for transcriptional induction. Chromatin immunoprecipitation studies also demonstrated that HIF2α binds to the Atp7a promoter region. Lastly, Atp7a and HIF2α protein levels were shown to be increased by both treatments. In conclusion, the Atp7a gene is upregulated by direct interaction with HIF2α, demonstrating coordinate regulation with genes related to intestinal iron homeostasis.
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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.