Title

Exposure to Silver Nanoparticles Inhibits Selenoprotein Synthesis and the Activity of Thioredoxin Reductase

Authors

Authors

M. Srivastava; S. Singh;W. T. Self

Comments

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Abbreviated Journal Title

Environ. Health Perspect.

Keywords

nanotoxicology; proliferation; selenium; selenocysteine; silver; nanoparticles; thioredoxin reductase; HUMAN HEPATOMA-CELLS; X-RAY-MICROANALYSIS; OXIDATIVE STRESS; GLUTATHIONE-PEROXIDASE; ENDOPLASMIC-RETICULUM; ARSENIC TRIOXIDE; DIFFERENT SIZES; IN-VITRO; APOPTOSIS; SELENIUM; Environmental Sciences; Public, Environmental & Occupational Health; Toxicology

Abstract

BACKGROUND: Silver nanoparticles (AgNPs) and silver (Ag)-based materials are increasingly being incorporated into consumer products, and although humans have been exposed to colloidal Ag in many forms for decades, this rise in the use of Ag materials has spurred interest into their toxicology. Recent reports have shown that exposure to AgNPs or Ag ions leads to oxidative stress, endoplasmic reticulum stress, and reduced cell proliferation. Previous studies have shown that Ag accumulates in tissues as silver sulfides (Ag2S) and silver selenide (Ag2Se). OBJECTIVES: In this study we investigated whether exposure of cells in culture to AgNPs or Ag ions at subtoxic doses would alter the effective metabolism of selenium, that is, the incorporation of selenium into selenoproteins. METHODS: For these studies we used a keratinocyte cell model (HaCat) and a lung cell model (A549). We also tested (in vitro, both cellular and chemical) whether Ag ions could inhibit the activity of a key selenoenzyme, thioredoxin reductase (TrxR). RESULTS: We found that exposure to AgNPs or far lower levels of Ag ions led to a dose-dependent inhibition of selenium metabolism in both cell models. The synthesis of protein was not altered under these conditions. Exposure to nanomolar levels of Ag ions effectively blocked selenium metabolism, suggesting that Ag ion leaching was likely the mechanism underlying observed changes during AgNP exposure. Exposure likewise inhibited TrxR activity in cultured cells, and Ag ions were potent inhibitors of purified rat TrxR isoform 1 (cytosolic) (TrxR1) enzyme. CONCLUSIONS: Exposure to AgNPs leads to the inhibition of selenoprotein synthesis and inhibition of TrxR1. Further, we propose these two sites of action comprise the likely mechanism underlying increases in oxidative stress, increases endoplasmic reticulum stress, and reduced cell proliferation during exposure to Ag.

Journal Title

Environmental Health Perspectives

Volume

120

Issue/Number

1

Publication Date

1-1-2012

Document Type

Article

Language

English

First Page

56

Last Page

61

WOS Identifier

WOS:000299650400026

ISSN

0091-6765

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