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

Journal Article · · Biochimica et Biophysica Acta - General Subjects
 [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
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); Australian Research Council (ARC)
Grant/Contract Number:
AC02-06CH11357; DP140100176
OSTI ID:
1476304
Alternate ID(s):
OSTI ID: 1724275
Journal Information:
Biochimica et Biophysica Acta - General Subjects, Vol. 1862, Issue 11; ISSN 0304-4165
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

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Cited By (3)

Development of a hydrolysis-based small-molecule hydrogen selenide (H 2 Se) donor journal January 2019
Toxicity of organochalcogens in human leukocytes is associated, but not directly related with reactive species production, apoptosis and changes in antioxidant gene expression journal October 2018
2019 atomic spectrometry update – a review of advances in X-ray fluorescence spectrometry and its special applications journal January 2019

Figures / Tables (17)

Scheme 1(p. 4)figure Scheme 1
Scheme 2(p. 6)figure Scheme 2
Figure-1(p. 11)figure Figure-1
Table 1(p. 11)table Table 1
Scheme 3(p. 12)figure Scheme 3
Figure 2(p. 13)figure Figure 2
Table 2(p. 13)table Table 2
Scheme 4(p. 14)figure Scheme 4
Scheme 5(p. 14)figure Scheme 5
Figure 3(p. 15)figure Figure 3
Table 3(p. 15)table Table 3
Table 4 (1)(p. 16)table Table 4 (1)
Scheme 6(p. 17)figure Scheme 6
Table 4 (2)(p. 17)table Table 4 (2)
Figure 4(p. 20)figure Figure 4
Table 5(p. 21)table Table 5
Figure 6(p. 22)figure Figure 6

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Related Subjects

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