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Journal of Environmental Pathology, Toxicology and Oncology
Главный редактор: Qian Peng (open in a new tab)

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ISSN Печать: 0731-8898

ISSN Онлайн: 2162-6537

The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) IF: 2.4 To calculate the five year Impact Factor, citations are counted in 2017 to the previous five years and divided by the source items published in the previous five years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) 5-Year IF: 2.8 The Immediacy Index is the average number of times an article is cited in the year it is published. The journal Immediacy Index indicates how quickly articles in a journal are cited. Immediacy Index: 0.5 The Eigenfactor score, developed by Jevin West and Carl Bergstrom at the University of Washington, is a rating of the total importance of a scientific journal. Journals are rated according to the number of incoming citations, with citations from highly ranked journals weighted to make a larger contribution to the eigenfactor than those from poorly ranked journals. Eigenfactor: 0.00049 The Journal Citation Indicator (JCI) is a single measurement of the field-normalized citation impact of journals in the Web of Science Core Collection across disciplines. The key words here are that the metric is normalized and cross-disciplinary. JCI: 0.59 SJR: 0.429 SNIP: 0.507 CiteScore™:: 3.9 H-Index: 49

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Regulation of Heme Synthesis and Proteasomal Activity by Copper: Possible Implications for Wilson's Disease

Том 28, Выпуск 3, 2009, pp. 209-221
DOI: 10.1615/JEnvironPatholToxicolOncol.v28.i3.20
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Краткое описание

Wilson's disease (Wd) is a genetic disorder resulting in Cu2+ accumulation, and is caused by mutations in the ATP7B gene, the copper transporter. In vivo studies show a correlation between Cu2+ accumulation and malfunction of the heme biosynthesis pathway. In this study, we describe multiple effects of Cu2+ accumulation on heme synthesis, which, in turn, affect proteasomal activity. Cu2+ toxicity was examined in two hepatocellular carcinoma cell lines, HepG2 and Hep3B, with Hep3B cells containing an integrated hepatitis B virus genome. Exposure of HepG2 and Hep3B cells to Cu2+ inhibited the enzymes PBGD and ALAD of the heme synthesis pathway and, in parallel, upregulated heme oxygenase-1 (HO-1). Proto-porphyrin IX (PpIX) and the heme pool were reduced as a result of these processes. PpIX synthesis was found to be lower in cells expressing the mutant ATP7B (P1134P), compared to those expressing the WT enzyme. Proteasomal activity was inhibited under Cu2+ treatment in HepG2 cells; however, Cu2+ induced marked proteosomal acceleration in Hep3B cells. Under these conditions, Ub-conjugated proteins were gradually accumulated, whereas treatment with bathocuproine disulfonic acid (BCS), a Cu2+ chelator, reversed this effect. In conclusion, our data suggest that copper downregulates the heme synthesis pathway in hepatocellular cells and further reduces it in the presence of mutated ATP7B.

Ключевые слова: ALAD, ATP7B, PBGD, proteasome, protoporphyrin IX, ubiquitin
ЦИТИРОВАНО В
  1. Nakayama Kenji, Katoh Yoshinobu, Tamura Mamoru, “Triple Observation Method (TOM)” to Discriminate Optically Autofluorescence from Porphyrins Versus that from Copper-Metallothioneins, Journal of Fluorescence, 21, 2, 2011. Crossref

  2. Matak Pavle, Zumerle Sara, Mastrogiannaki Maria, El Balkhi Souleiman, Delga Stephanie, Mathieu Jacques R. R., Canonne-Hergaux François, Poupon Joel, Sharp Paul A., Vaulont Sophie, Peyssonnaux Carole, Missirlis Fanis, Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice, PLoS ONE, 8, 3, 2013. Crossref

  3. Lukas Jan, Pospech Jola, Oppermann Christina, Hund Christina, Iwanov Katharina, Pantoom Supansa, Petters Janine, Frech Moritz, Seemann Susanne, Thiel Franziska-Gisela, Modenbach Jana-Marielle, Bolsmann Robert, de Freitas Chama Laura, Kraatz Franziska, El-Hage Firas, Gronbach Manuel, Klein Annelie, Müller Regina, Salloch Sabine, Weiss Frank-Ulrich, Simon Peter, Wagh Preshit, Klemenz Almuth, Krüger Elke, Mayerle Julia, Delcea Mihaela, Kragl Udo, Beller Matthias, Rolfs Arndt, Lerch Markus M., Sendler Matthias, Role of endoplasmic reticulum stress and protein misfolding in disorders of the liver and pancreas, Advances in Medical Sciences, 64, 2, 2019. Crossref

  4. Song In-ho, Torawane Pritam, Lee Jung-Seop, Warkad Shrikant Dashrath, Borase Amulrao, Sahoo Suban K., Nimse Satish Balasaheb, Kuwar Anil, The detection of Al3+ and Cu2+ ions using isonicotinohydrazide-based chemosensors and their application to live-cell imaging, Materials Advances, 2, 19, 2021. Crossref

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