title: Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.
abstract: Proteomics 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 cell-cell 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.
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Jijing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Jing
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Heidi Qunhui
authors.initials: HQ
authors.lastname: Xie
authors.affiliation: JMP Life Sciences, SAS Institute, Cary, NC 27513, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, CA 95616-8588, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Rice
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: binzhao@rcees.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Guibin
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D020261:Arsenic Poisoning / Q000150:complications / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D051183:Desmoglein 1 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053553:Keratin-6 / Q000235:genetics / Q000378:metabolism*; D007642:Keratosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers; C495297:DSG1 protein, human; D051183:Desmoglein 1; C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; C507571:KRT6C protein, human; D053553:Keratin-6
keywords: Arsenic; Biomarker; Human epidermis; Proteomic; Skin keratosis