ArticleJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry2012
Synchrotron radiation induced X-ray emission studies of the antioxidant mechanism of the organoselenium drug ebselen.
Article in Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Synchrotron X-Ray Fluorescence Nanoprobe Reveals Target Sites for Organo-Osmium Complex in Human Ovarian Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- Correction to "Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator".ACS medicinal chemistry letters · 2016Article
- Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator.ACS medicinal chemistry letters · 2014Article
- Elemental and chemically specific X-ray fluorescence imaging of biological systems.Chemical reviews · 2014Review
- Ebselen, a promising antioxidant drug: mechanisms of action and targets of biological pathways.Molecular biology reports · 2014Review
- X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder.Chemical science · 2014Article
- Review
- Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers.Journal of medicinal chemistry · 2013Review
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Authors and funding
9 authors at 7 institutions in 4 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Synchrotron radiation induced X-ray emission (SRIXE) spectroscopy was used to map the cellular uptake of the organoselenium-based antioxidant drug ebselen using differentiated ND15 cells as a neuronal model. The cellular SRIXE spectra, acquired using a hard X-ray microprobe beam (12.8-keV), showed a large enhancement of fluorescence at the K(α) line for Se (11.2-keV) following treatment with ebselen (10 μM) at time periods from 60 to 240 min. Drug uptake was quantified and ebselen was shown to induce time-dependent changes in cellular elemental content that were characteristic of oxidative stress with the efflux of K, Cl, and Ca species. The SRIXE cellular Se distribution map revealed that ebselen was predominantly localized to a discreet region of the cell which, by comparison with the K and P elemental maps, is postulated to correspond to the endoplasmic reticulum. On the basis of these findings, it is hypothesized that a major outcome of ebselen redox catalysis is the induction of cellular stress. A mechanism of action of ebselen is proposed that involves the cell responding to drug-induced stress by increasing the expression of antioxidant genes. This hypothesis is supported by the observation that ebselen also regulated the homeostasis of the transition metals Mn, Cu, Fe, and Zn, with increases in transition metal uptake paralleling known induction times for the expression of antioxidant metalloenzymes.
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