Decreased Urinary Beta-Defensin-1 Expression as a Biomarker of Response to Arsenic

Hegedus, Christine; Skibola, Christine F.; Warner, Malcolm; Skibola, Danica R.; Alexander, David B.; Lim, Sophia; Dangleben, Nygerma L.; Zhang, Luoping; Clark, Michael E.; Pfeiffer, Ruth M.; Steinmaus, Craig; Smith, Allan H.; Smith, Martyn T.; Moore, Lee E.

doi:10.1093/toxsci/kfn104

Cited by 30 publications

(25 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Examination of the urinary proteome in a human population exposed to As revealed decreased expression of human β-defensin-1 (HBD-1) peptides in the urine of men with high As exposure from Nevada (Hegedus et al, 2008). We replicated these findings in a second, independent As exposed population from Chile, and validated the relationship between As exposure and HBD-1 in vitro.…”

Section: Proteomic Biomarkers Of Arsenic Exposuresupporting

confidence: 52%

“…As with transcriptomics, proteomic studies of human-exposed populations are currently limited and include studies by our group and others of populations exposed to benzene and arsenic (Zhai et al, 2005;Harezlak et al, 2008;Hegedus et al, 2008). Advances are continuing to be made in the discovery of protein biomarkers of disease (Hanash et al, 2008;Howes et al, 2008), which together with exposure-related proteomic profiles will facilitate an understanding of disease mechanisms.…”

Section: Proteomicsmentioning

confidence: 99%

See 1 more Smart Citation

Toxicogenomic Studies in Human Populations

McHale

Zhang

Hubbard

et al. 2011

Applications of Toxicogenomics in Safety Evaluation and Risk Assessment

Self Cite

View full text Add to dashboard Cite

Section: Proteomic Biomarkers Of Arsenic Exposuresupporting

confidence: 52%

Section: Proteomicsmentioning

confidence: 99%

Toxicogenomic Studies in Human Populations

McHale

Zhang

Hubbard

et al. 2011

Applications of Toxicogenomics in Safety Evaluation and Risk Assessment

Self Cite

View full text Add to dashboard Cite

“…In addition, two recent studies demonstrated the significant potentials of mass spectrometry proteomics to identify the arsenic biomarkers of effect. Hegedus et al (2008) conducted urine proteomic analyses and observed that in highly arsenic exposed men (well water >500 µg arsenic/L), there was an increased level of human β-defensin-1 (HBD-1). Harezlak et al (2008) showed significant associations of arsenic exposure to either under-or over-expression of 20 proteins in the plasma of highly arsenic exposed study participants selected from a large arsenic case control study of skin disease in Bangladesh.…”

Section: Biomarkers Of Effectmentioning

confidence: 99%

Scientific Opinion on Arsenic in Food

2009

EFSA Journal

857

220

View full text Add to dashboard Cite

The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks to human health related to the presence of arsenic in food. More than 100,000 occurrence data on arsenic in food were considered with approximately 98 % reported as total arsenic. Making a number of assumptions for the contribution of inorganic arsenic to total arsenic, the inorganic arsenic exposure from food and water across 19 European countries, using lower bound and upper bound concentrations, has been estimated to range from 0.13 to 0.56 µg/kg bodyweight (b.w.) per day for average consumers, and from 0.37 to 1.22 µg/kg b.w. per day for 95 th percentile consumers. Dietary exposure to inorganic arsenic for children under three years of age is in general estimated to be from 2 to 3-fold that of adults. The CONTAM Panel concluded that the provisional tolerable weekly intake (PTWI) of 15 µg/kg b.w. established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) is no longer appropriate as data had shown that inorganic arsenic causes cancer of the lung and urinary bladder in addition to skin, and that a range of adverse effects had been reported at exposures lower than those reviewed by the JECFA. The CONTAM Panel modelled the dose-response data from key for providing consumption information and calculating exposure, the partners of the EFSA project on the "Individual food consumption data and exposure" coordinated by Ghent University (Department of Public Health, University Hospital, Ghent University, Belgium), and RIKILT (Institute of Food Safety, Wageningen, The Netherlands) for the accessibility of the exposure assessment tools. 4 Table of contents shows now the fourth level of subheadings. 5 An error in the interpretation of the total number of the population in the study of Rahman et al. (2006a) was discovered (Table 41). The BMDL was recalculated and as a consequence it was not considered a potential reference point. The text in the opinion, Table 43 and Appendix were revised accordingly. In addition, the header of the "total number of cases" was replaced by "total number of individuals" in Tables 40-42 and the erroneous units were corrected to µg/L in the text below SUMMARYArsenic is a metalloid that occurs in different inorganic and organic forms, which are found in the environment both from natural occurrence and from anthropogenic activity. The inorganic forms of arsenic are more toxic as compared to the organic arsenic but so far most of the occurrence data in food collected in the framework of official food control are still reported as total arsenic without differentiating the various arsenic species. The need for speciation data is evident because several investigations have shown that especially in seafood most of the arsenic is present in organic forms that are less toxic. Consequently, a risk assessment not taking into account the different species but considering total arsenic as being present exclusively as inorganic arsenic would lead to a considerable overestimation of the health risk rel...

show abstract

“…Previous studies have analyzed arsenic-exposed human serum and urinary proteomic profiles and identified several potential biomarkers (Harezlak et al, 2008;Hegedus et al, 2008;Zhai et al, 2005). According to the IARC, skin shows the strongest association between chronic arsenic exposure and cancer (IARC, 2004), and dermal manifestations such as hyperpigmentation and hyperkeratosis are diagnostic of chronic arsenicosis.…”

Section: Introductionmentioning

confidence: 99%

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis

Guo

Tian

et al. 2016

Environmental Pollution

View full text Add to dashboard Cite

a b s t r a c tProteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cellcell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure.

show abstract

Decreased Urinary Beta-Defensin-1 Expression as a Biomarker of Response to Arsenic

Cited by 30 publications

References 33 publications

Toxicogenomic Studies in Human Populations

Toxicogenomic Studies in Human Populations

Scientific Opinion on Arsenic in Food

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis

Contact Info

Product

Resources

About