Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM
Abstract
A variety of selenium compounds have been observed to provide protection against oxidative stress, presumably by mimicking the mechanism of action of the glutathione peroxidases. However, the selenium chemistry that underpins the action of these compounds has not been unequivocally established. The synchrotron based techniques, X-ray absorption spectroscopy and X-ray fluorescence microscopy were used to examine the cellular speciation and distribution of selenium in SH-SY5Y cells pretreated with one of two diphenyl diselenides, or ebselen, followed by peroxide insult. Bis(2-aminophenyl)diselenide was shown to protect against oxidative stress conditions which mimic ischemic strokes, while its nitro analogue, bis(2-nitrophenyl)diselenide did not. This protective activity was tentatively assigned to the reductive cleavage of bis(2-aminophenyl)diselenide inside human neurocarcinoma cells, SH-SY5Y, while bis(2-nitrophenyl)diselenide remained largely unchanged. The distinct chemistries of the related compounds were traced by the changes in selenium speciation in bulk pellets of treated SH-SY5Y cells detected by X-ray absorption spectroscopy. Further, bis(2-aminophenyl)diselenide, like the known stroke mitigation agent ebselen, was observed by X-ray fluorescence imaging to penetrate into the nucleus of SH-SY5Y cells while bis(2-nitrophenyl)diselenide was observed to be excluded from the nuclear region. The differences in activity were thus attributed to the varied speciation and cellular localisation of the compounds, ormore »
- Authors:
-
- Univ. of Adelaide, SA (Australia). Dept. of Chemistry
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS) and X-ray Science Division
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); Australian Research Council (ARC)
- OSTI Identifier:
- 1476304
- Alternate Identifier(s):
- OSTI ID: 1724275
- Grant/Contract Number:
- AC02-06CH11357; DP140100176
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biochimica et Biophysica Acta - General Subjects
- Additional Journal Information:
- Journal Volume: 1862; Journal Issue: 11; Journal ID: ISSN 0304-4165
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; Selenium; diphenyl diselenide; ebselen; oxidative stress; X-ray absorption spectroscopy; X-ray fluorescence microscopy
Citation Formats
Wedding, Jason L., Lai, Barry, Vogt, Stefan, and Harris, Hugh H. Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM. United States: N. p., 2018.
Web. doi:10.1016/j.bbagen.2018.03.031.
Wedding, Jason L., Lai, Barry, Vogt, Stefan, & Harris, Hugh H. Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM. United States. https://doi.org/10.1016/j.bbagen.2018.03.031
Wedding, Jason L., Lai, Barry, Vogt, Stefan, and Harris, Hugh H. Sat .
"Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM". United States. https://doi.org/10.1016/j.bbagen.2018.03.031. https://www.osti.gov/servlets/purl/1476304.
@article{osti_1476304,
title = {Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM},
author = {Wedding, Jason L. and Lai, Barry and Vogt, Stefan and Harris, Hugh H.},
abstractNote = {A variety of selenium compounds have been observed to provide protection against oxidative stress, presumably by mimicking the mechanism of action of the glutathione peroxidases. However, the selenium chemistry that underpins the action of these compounds has not been unequivocally established. The synchrotron based techniques, X-ray absorption spectroscopy and X-ray fluorescence microscopy were used to examine the cellular speciation and distribution of selenium in SH-SY5Y cells pretreated with one of two diphenyl diselenides, or ebselen, followed by peroxide insult. Bis(2-aminophenyl)diselenide was shown to protect against oxidative stress conditions which mimic ischemic strokes, while its nitro analogue, bis(2-nitrophenyl)diselenide did not. This protective activity was tentatively assigned to the reductive cleavage of bis(2-aminophenyl)diselenide inside human neurocarcinoma cells, SH-SY5Y, while bis(2-nitrophenyl)diselenide remained largely unchanged. The distinct chemistries of the related compounds were traced by the changes in selenium speciation in bulk pellets of treated SH-SY5Y cells detected by X-ray absorption spectroscopy. Further, bis(2-aminophenyl)diselenide, like the known stroke mitigation agent ebselen, was observed by X-ray fluorescence imaging to penetrate into the nucleus of SH-SY5Y cells while bis(2-nitrophenyl)diselenide was observed to be excluded from the nuclear region. The differences in activity were thus attributed to the varied speciation and cellular localisation of the compounds, or their metabolites, as detected by X-ray absorption spectroscopy and X-ray fluorescence microscopy. The significance of this work is, for the first time, the protective action of selenium compounds against redox stress with particular chemical speciation using a direct measurement approach.},
doi = {10.1016/j.bbagen.2018.03.031},
journal = {Biochimica et Biophysica Acta - General Subjects},
number = 11,
volume = 1862,
place = {United States},
year = {Sat Apr 07 00:00:00 EDT 2018},
month = {Sat Apr 07 00:00:00 EDT 2018}
}
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Figures / Tables:
Scheme 1: Summary of previously proposed modes of action for ebselen’s glutathione peroxidase activity reacting with both hydrogen peroxide and organic thiols such as glutathione (RSH).
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