Affordable Access

Publisher Website

Diphenyl diselenide and analogs are substrates of cerebral rat thioredoxin reductase: A pathway for their neuroprotective effects

Authors
Journal
Neuroscience Letters
0304-3940
Publisher
Elsevier
Publication Date
Volume
503
Issue
1
Identifiers
DOI: 10.1016/j.neulet.2011.07.050
Keywords
  • Thioredoxin Reductase (Trxr)
  • Selenium Compounds
  • Ebselen
  • Diphenyl Diselenide
Disciplines
  • Biology

Abstract

Abstract Thioredoxin reductase (TrxR) isoforms play important roles in cell physiology, protecting cells against oxidative processes. In addition to its endogenous substrates (Trx isoforms), hepatic TrxR can reduce organic selenium compounds such as ebselen and diphenyl diselenide to their selenol intermediates, which can be involved in their hepatoprotective properties. Taking this into account, the aim of the present study was to evaluate the hypothesis that ebselen, diphenyl diselenide and its analogs (4,4′-bistrifluoromethyldiphenyl diselenide, 4,4′-bismethoxydiphenyl diselenide, 4.4′-biscarboxy-diphenyl diselenide, 4,4′-bischlorodiphenyl diselenide, 2,4,6,2′,4′,6′-hexamethyldiphenyl diselenide) could be substrates of rat brain TrxR. In the presence of partially purified rat brain TrxR, diphenyl diselenide, bismethoxydiphenyl diselenide and bischlorodiphenyl diselenide (at 10, 15 and 20μM) stimulated NADPH oxidation, indicating that they are substrates of brain TrxR. In contrast, ebselen and bistrifluoromethyldiphenyl diselenide, that have been previously demonstrated to be substrate of hepatic TrxR, were not reduced by rat brain TrxR. The results presented here suggest that diphenyl diselenide can exert neuroprotective effects by mimicking glutathione peroxidase activity and also via its reduction by TrxR. However, ebselen was not reduced by brain TrxR, indicating that the neuroprotective properties of this compound is possibly mediate by its glutathione peroxidase-like activity.

There are no comments yet on this publication. Be the first to share your thoughts.