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Title: 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 » 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:
Research Org.:
Argonne National Lab. (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 = {2018},
month = {4}
}

Journal Article:

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Cited by: 2 works
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Figures / Tables:

Scheme 1 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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Works referenced in this record:

Phospholipase A 2 , Hydroxyl Radicals, and Lipid Peroxidation in Transient Cerebral Ischemia
journal, October 2003

  • Adibhatla, Rao Muralikrishna; Hatcher, James F.; Dempsey, Robert J.
  • Antioxidants & Redox Signaling, Vol. 5, Issue 5
  • DOI: 10.1089/152308603770310329

Oxidative Stress and Its Role in the Pathogenesis of Ischaemic Stroke
journal, December 2009


Some new prospects in the understanding of the molecular basis of the pathogenesis of stroke
journal, July 2007

  • Saeed, Sheikh Arshad; Shad, Kaneez Fatima; Saleem, Taimur
  • Experimental Brain Research, Vol. 182, Issue 1
  • DOI: 10.1007/s00221-007-1050-9

Pathophysiology of ischaemia-reperfusion injury
journal, February 2000


Cytidine 5?-Diphosphocholine (CDP-Choline) in Stroke and Other CNS Disorders
journal, January 2005


Treatment of Acute Ischemic Stroke
journal, September 2000


Salvaging The Ischaemic Penumbra: More Than Just Reperfusion?
journal, January 2002

  • Phan, Thanh G.; Wright, Peter M.; Markus, Romesh
  • Clinical and Experimental Pharmacology and Physiology, Vol. 29, Issue 1-2
  • DOI: 10.1046/j.1440-1681.2002.03609.x

Oxygen Radicals in Focal Cerebral Ischemia
journal, January 1994


Ebselen in Acute Ischemic Stroke: A Placebo-Controlled, Double-blind Clinical Trial
journal, January 1998


Ebselen in Acute Middle Cerebral Artery Occlusion: A Placebo-Controlled, Double-Blind Clinical Trial
journal, January 1999

  • Ogawa, Akira; Yoshimoto, Takashi; Kikuchi, Haruhiko
  • Cerebrovascular Diseases, Vol. 9, Issue 2
  • DOI: 10.1159/000015908

Organochalcogen peroxidase mimetics as potential drugs: a long story of a promise still unfulfilled
journal, January 2014


Electrochemical, in vitro and cell culture analysis of integrated redox catalysts: implications for cancer therapy
journal, January 2003

  • Giles, Gregory I.; Giles, Niroshini M.; Collins, Catriona A.
  • Chemical Communications, Issue 16
  • DOI: 10.1039/b302877a

Catalytic effects of glutathione peroxidase mimetics on the thiol reduction of cytochrome c
journal, November 1994


Determination of the relative contributions of the diselenide and selenol forms of ebselen in the mechanism of its glutathione peroxidase-like activity
journal, September 1992


Ebselen, a selenoorganic compound as glutathione peroxidase mimic
journal, March 1993


Mechanism of the Catalytic Reduction of Hydroperoxides by Ebselen : A Selenium - 77 Nmr Study
journal, January 1987

  • Fischer, Hartmut; Dereu, Norbert
  • Bulletin des Sociétés Chimiques Belges, Vol. 96, Issue 10
  • DOI: 10.1002/bscb.19870961006

A novel biologically active seleno-organic compound—II
journal, October 1984


Characterisation and quantitation of a selenol intermediate in the reaction of ebselen with thiols
journal, September 1992


Glutathione Peroxidase (GPx)-like Antioxidant Activity of the Organoselenium Drug Ebselen:  Unexpected Complications with Thiol Exchange Reactions
journal, August 2005

  • Sarma, Bani Kanta; Mugesh, G.
  • Journal of the American Chemical Society, Vol. 127, Issue 32
  • DOI: 10.1021/ja052794t

Kinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ51)
journal, June 1988


A Novel Antioxidant Mechanism of Ebselen Involving Ebselen Diselenide, a Substrate of Mammalian Thioredoxin and Thioredoxin Reductase
journal, October 2002


Ebselen: A substrate for human thioredoxin reductase strongly stimulating its hydroperoxide reductase activity and a superfast thioredoxin oxidant
journal, June 2002

  • Zhao, R.; Masayasu, H.; Holmgren, A.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 13
  • DOI: 10.1073/pnas.122061399

Development of synthetic compounds with glutathione peroxidase activity
journal, July 1989

  • Wilson, Stephen R.; Zucker, Paul A.; Huang, Ruey Ruey C.
  • Journal of the American Chemical Society, Vol. 111, Issue 15
  • DOI: 10.1021/ja00197a065

Diphenyl diselenide, a simple organoselenium compound, decreases methylmercury-induced cerebral, hepatic and renal oxidative stress and mercury deposition in adult mice
journal, April 2009


Efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice
journal, September 2007


Oral administration of diphenyl diselenide protects against cadmium-induced liver damage in rats
journal, January 2008

  • Borges, Lysandro Pinto; Brandão, Ricardo; Godoi, Benhur
  • Chemico-Biological Interactions, Vol. 171, Issue 1
  • DOI: 10.1016/j.cbi.2007.09.005

Passive smoke exposure induces oxidative damage in brains of rat pups: Protective role of diphenyl diselenide
journal, August 2009

  • Stangherlin, Eluza Curte; Luchese, Cristiane; Ardais, Ana Paula
  • Inhalation Toxicology, Vol. 21, Issue 10
  • DOI: 10.1080/08958370802526881

Diphenyl diselenide protects against glycerol-induced renal damage in rats
journal, October 2009

  • Brandão, Ricardo; Acker, Carmine I.; Leite, Marlon R.
  • Journal of Applied Toxicology, Vol. 29, Issue 7
  • DOI: 10.1002/jat.1449

Anti-inflammatory and antinociceptive activity of diphenyl diselenide
journal, February 2003

  • Nogueira, C. W.; Quinhones, E. B.; Jung, E. A. C.
  • Inflammation Research, Vol. 52, Issue 2
  • DOI: 10.1007/s000110300001

Antisecretory and antiulcer effects of diphenyl diselenide
journal, January 2006

  • Savegnago, Lucielli; Trevisan, Marcio; Alves, Diego
  • Environmental Toxicology and Pharmacology, Vol. 21, Issue 1
  • DOI: 10.1016/j.etap.2005.07.017

Diphenyl diselenide prevents methylmercury-induced mitochondrial dysfunction in rat liver slices
journal, December 2012

  • Dalla Corte, Cristiane L.; Soares, Félix A. A.; Aschner, Michael
  • Tetrahedron, Vol. 68, Issue 51
  • DOI: 10.1016/j.tet.2012.09.025

Diphenyl diselenide a janus-faced molecule
journal, January 2010


Diphenyl diselenide induces apoptotic cell death and modulates ERK1/2 phosphorylation in human neuroblastoma SH-SY5Y cells
journal, October 2010

  • Posser, Thaís; de Paula, Mariane Trindade; Franco, Jeferson Luis
  • Archives of Toxicology, Vol. 85, Issue 6
  • DOI: 10.1007/s00204-010-0602-0

Investigations into the potential neurotoxicity induced by diselenides in mice and rats
journal, February 2003


The Central Role of Metal Coordination in Selenium Antioxidant Activity
journal, January 2006

  • Battin, Erin E.; Perron, Nathan R.; Brumaghim, Julia L.
  • Inorganic Chemistry, Vol. 45, Issue 2
  • DOI: 10.1021/ic051594f

Rapid colorimetric assay for cell growth and survival
journal, May 1986


The Accuracy of Estimation of Hydrogen Peroxide by Potassium Permanganate Titration
journal, April 1948

  • Huckaba, Charles E.; Keyes, Frederick G.
  • Journal of the American Chemical Society, Vol. 70, Issue 4
  • DOI: 10.1021/ja01184a098

A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture
journal, August 1995


MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants
journal, January 2001

  • Buckman, Jennifer F.; Hernández, Hélène; Kress, Geraldine J.
  • Journal of Neuroscience Methods, Vol. 104, Issue 2
  • DOI: 10.1016/S0165-0270(00)00340-X

Detoxification of exogenous hydrogen peroxide and organic hydroperoxides by cultured astroglial cells assessed by microtiter plate assay
journal, March 1998


Cytotoxic potency of H2O2 in cell cultures: Impact of cell concentration and exposure time
journal, November 2010


Assessment of cell death studies by monitoring hydrogen peroxide in cell culture
journal, July 2014


Exposure to hydrogen peroxide induces cell death via apoptosis in cultured rat cortical neurons
journal, January 1994


Elevations in cytosolic free Ca2+ are not required to trigger apoptosis in human leukaemia cells
journal, March 1992


Bcl-2 functions in an antioxidant pathway to prevent apoptosis
journal, October 1993


Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species
journal, November 1993


Pharmacology and toxicology of diphenyl diselenide in several biological models
journal, August 2007


The crystal structure of diphenyl diselenide
journal, July 1952


Structure of bis(p-nitrophenyl) diselenide at 187 K
journal, October 1986

  • Morris, G. D.; Einstein, F. W. B.
  • Acta Crystallographica Section C Crystal Structure Communications, Vol. 42, Issue 10
  • DOI: 10.1107/S0108270186092004

Direct synthesis of 2-aryl-1,3-benzoselenazoles by reaction of bis(2-aminophenyl) diselenides with aryl aldehydes using sodium metabisulfite
journal, January 2013

  • Radatz, Cátia Schwartz; Alves, Diego; Schneider, Paulo Henrique
  • Tetrahedron, Vol. 69, Issue 4
  • DOI: 10.1016/j.tet.2012.11.091

Zinc-finger proteins
journal, February 1993


Apoptotic vs. Nonapoptotic Cytotoxicity Induced by Hydrogen Peroxide
journal, January 1997


Calcium signaling and apoptosis
journal, May 2003

  • Hajnóczky, György; Davies, Erika; Madesh, Muniswamy
  • Biochemical and Biophysical Research Communications, Vol. 304, Issue 3
  • DOI: 10.1016/S0006-291X(03)00616-8

Role of store-dependent influx of Ca2+ and efflux of K+ in apoptosis of CHO cells
journal, November 2004


Synchrotron radiation induced X-ray emission studies of the antioxidant mechanism of the organoselenium drug ebselen
journal, February 2012

  • Aitken, Jade B.; Lay, Peter A.; Duong, T. T. Hong
  • JBIC Journal of Biological Inorganic Chemistry, Vol. 17, Issue 4
  • DOI: 10.1007/s00775-012-0879-y

Works referencing / citing this record:

Development of a hydrolysis-based small-molecule hydrogen selenide (H 2 Se) donor
journal, January 2019

  • Newton, Turner D.; Pluth, Michael D.
  • Chemical Science, Vol. 10, Issue 46
  • DOI: 10.1039/c9sc04616j

2019 atomic spectrometry update – a review of advances in X-ray fluorescence spectrometry and its special applications
journal, January 2019

  • Vanhoof, Christine; Bacon, Jeffrey R.; Ellis, Andrew T.
  • Journal of Analytical Atomic Spectrometry, Vol. 34, Issue 9
  • DOI: 10.1039/c9ja90042j