ArticleThe Biochemical journal2007
Regulation of ceruloplasmin in human hepatic cells by redox active copper: identification of a novel AP-1 site in the ceruloplasmin gene.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Accurate quantification of cell-free Ceruloplasmin mRNA as a biomarker for early detection of hepatocellular carcinoma.Scientific reports · 2025Article
- Quantitative proteomics and RNA-sequencing of mouse liver endothelial cells identify novel regulators of BMP6 by iron.iScience · 2023Article
- The biology of mammalian multi-copper ferroxidases.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- A role for ceruloplasmin in the control of human glioblastoma cell responses to radiation.BMC cancer · 2022Article
- Correlations Among mRNA Expression Levels of ATP7A, Serum Ceruloplasmin Levels, and Neuronal Metabolism in Unmedicated Major Depressive Disorder.The international journal of neuropsychopharmacology · 2020Article
- Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades.Frontiers in immunology · 2018Article
- Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper.Bioscience reports · 2013Review
- Ototoxic Model of Oxaliplatin and Protection from Nicotinamide Adenine Dinucleotide.Journal of otology · 2013Article
- Effects of Copper and/or Cholesterol Overload on Mitochondrial Function in a Rat Model of Incipient Neurodegeneration.International journal of Alzheimer's disease · 2013Article
- A mouse mammary gland involution mRNA signature identifies biological pathways potentially associated with breast cancer metastasis.Journal of mammary gland biology and neoplasia · 2009Review
- Sera proteomic biomarker profiling in HIV-1 infected subjects with cognitive impairment.Proteomics. Clinical applications · 2008Article
- Hyaluronan regulates ceruloplasmin production by gliomas and their treatment-resistant multipotent progenitors.Journal of child neurology · 2008Article
- The uptake and fate of vanadyl ion in ascidian blood cells and a detailed hypothesis for the mechanism and location of biological vanadium reduction. A visible and X-ray absorption spectroscopic study.Journal of inorganic biochemistry · 2008Article
- The antioxidant response induced by Lonicera caerulaea berry extracts in animals bearing experimental solid tumors.Molecules (Basel, Switzerland) · 2008Article
- Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse.BMC genomics · 2007Article
- Intrapulmonary administration of purified NEIL2 abrogates NF-κB-mediated inflammation.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cp (ceruloplasmin), a copper containing plasma protein, mainly synthesized in the liver, is known to be functional between the interface of iron and copper metabolism. We have reported previously that Cp is regulated by cellular iron status, but the process of the regulation of Cp by copper still remains a subject for investigation. In the present paper, we show that PDTC (pyrrolidine dithiocarbamate), a thiol compound widely known to increase intracellular redox copper, regulates Cp expression in hepatic cells by a copper-dependent transcriptional mechanism. To find out the mechanism of induction, chimeric constructs of the Cp 5'-flanking region driving luciferase were transfected into human hepatic cells. Deletion and mutational analyses showed the requirement of a novel APRE [AP-1 (activator protein-1) responsive element] present about 3.7 kb upstream of the translation initiation site. The role of AP-1 was confirmed by electrophoretic mobility-shift analysis. Western blot and overexpression studies detected the AP-1 as a heterodimer of c-jun and c-fos proteins. The activation of AP-1 was found to be copper-dependent as a specific extracellular chelator bathocuproine disulfonic acid blocked PDTC-mediated induction of AP-1-DNA binding and increased reporter gene activity. Whereas, in a copper-free medium, PDTC failed to activate either AP-1 or Cp synthesis, supplementation of copper could reverse AP-1 activation and Cp synthesis. Our finding is not only the first demonstration of regulation of Cp by redox copper but may also explain previous findings of increased Cp expression in cancers like hepatocarcinoma, where the intracellular copper level is higher in a redox compromised environment.
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