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Title: Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM

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 » 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.« less
Authors:
 [1] ;  [2] ;  [2] ;  [1]
  1. Univ. of Adelaide, SA (Australia). Dept. of Chemistry
  2. Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS) and X-ray Science Division
Publication Date:
Grant/Contract Number:
AC02-06CH11357; DP140100176
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
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); Australian Research Council (ARC)
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
OSTI Identifier:
1476304

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., 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. doi:10.1016/j.bbagen.2018.03.031.
Wedding, Jason L., Lai, Barry, Vogt, Stefan, and Harris, Hugh H.. 2018. "Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM". United States. doi: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 = {2018},
month = {4}
}