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Type: Journal article
Title: Synchrotron radiation induced X-ray emission studies of the antioxidant mechanism of the organoselenium drug ebselen
Author: Aitken, J.
Lay, P.
Duong, T.
Aran, R.
Witting, P.
Harris, H.
Lai, B.
Vogt, S.
Giles, G.
Citation: Journal of Biological Inorganic Chemistry, 2012; 17(4):589-598
Publisher: Springer-Verlag
Issue Date: 2012
ISSN: 0949-8257
Statement of
Jade B. Aitken, Peter A. Lay, T. T. Hong Duong, Roshanak Aran, Paul K. Witting, Hugh H. Harris, Barry Lai, Stefan Vogt, Gregory I. Giles
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.
Keywords: Antioxidant; Drug; Ebselen; Organoselenium; Synchrotron-radiation-induced X-ray emission
Rights: © SBIC 2012
RMID: 0020118465
DOI: 10.1007/s00775-012-0879-y
Appears in Collections:Chemistry and Physics publications
IPAS publications
Environment Institute publications

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