Science Inventory

Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress

Citation:

Wages, P., L. Katelyn, Z. Zhang, W. Cheng, C. Elizabeth, A. Gold, P. Bromberg, Steve Simmons, AND J. Samet. Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, 28(12):2411-18, (2015).

Impact/Purpose:

This is an in vitro study examining a molecular initiating event that can lead to adverse health effects of exposure of air pollutants. The results of this study demonstrate for the first time that exposure to a ubiquitous air pollutant results in a specific type of oxidative modification of regulatory proteins in human lung cells. The study results are significant in that they identify a novel initiating event that may be generalizable to a wide variety of chemical agents that act as oxidant stressors, a common mechanism of action in toxicology.

Description:

Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental chemicals such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ)induce oxidative stress by redox cycling, which generates hydrogen peroxide (H202). Cysteinylthiolate residues on regulatory proteins are subjected to oxidative modification by H202 in physiological contexts and are also toxicological targets of oxidant stress induced by environmental contaminants. We investigated whether exposure to environmentally relevant concentrations of 1,2-NQ can induce H202-dependent oxidation of cysteinyl thiols in regulatory proteins as a readout of oxidant stress in human airway epithelial cells. BEAS-28 cells were exposed to 0-1000 μM 1,2-NQ for 0-30 min, and levels of H202 were measured by ratiometric spectrofluorometry of HyPer. H202-dependent protein sulfenylation was measured using immunohistochemistry, immunoblotting, and isotopic mass spectrometry. Catalase overexpression was used to investigate the relationship between H202 generation and protein sulfenylation in cells exposed to 1,2-NQ. Multiple experimental approaches showed that exposure to 1,2-NQ at concentrations as low as 3 μM induces H202-dependent protein sulfenylation in BEAS-28 cells. Moreover, the time of onset and duration of 1,2-NQ-induced sulfenylation of the regulatory proteins GAP DH and PTP1B showed significant differences. Oxidative modification of regulatory cysteinyl thiols in human lung cells exposed to relevant concentrations of an ambient air contaminant represents a novel marker of oxidative environmental stress.

URLs/Downloads:

http://dx.doi.org/10.1021/acs.chemrestox.5b00424   Exit

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 11/25/2015
Record Last Revised: 11/27/2017
OMB Category: Other
Record ID: 316810

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

ENVIRONMENTAL PUBLIC HEALTH DIVISION

CLINICAL RESEARCH BRANCH