SILAC-based quantitative proteomic analysis revealswidespread molecular alterations in human skinkeratinocytes upon chronic arsenic exposure

Ahmad M, Sartaj and Pinto, Sneha M. and Paul, Somnath and Raja, Remya and Nanjappa, Vishalakshi and Syed, Nazia and Advani, Jayshree and Renuse, Santosh and Sahasrabuddhe, Nandini A and Keshava Prasad, T. S and Giri, Ashok K and Gowda, Harsha and Chatterjee, Aditi (2017) SILAC-based quantitative proteomic analysis revealswidespread molecular alterations in human skinkeratinocytes upon chronic arsenic exposure. PROTEOMICS, 17 (6). 01-14.

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    Abstract

    Chronic exposure to arsenic is associated with dermatological and nondermatological disor-ders. Consumption of arsenic-contaminated drinking water results in accumulation of arsenicin liver, spleen, kidneys, lungs, and gastrointestinal tract. Although arsenic is cleared from thesesites, a substantial amount of residual arsenic is left in keratin-rich tissues including skin. Epi-demiological studies suggest the association of skin cancer upon arsenic exposure, however,the mechanism of arsenic-induced carcinogenesis is not completely understood. We developeda cell line based model to understand the molecular mechanisms involved in arsenic-mediatedtoxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT, was chronically ex-posed to 100 nM sodium arsenite over a period of 6 months. We observed an increase in basalROS levels in arsenic-exposed cells. SILAC-based quantitative proteomics approach resultedin identification of 2111 proteins of which 42 proteins were found to be overexpressed and 54downregulated (twofold) upon chronic arsenic exposure. Our analysis revealed arsenic-inducedoverexpression of aldo-keto reductase family 1 member C2 (AKR1C2), aldo-keto reductase fam-ily 1 member C3 (AKR1C3), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)Hdehydrogenase [quinone] 1 (NQO1) among others. We observed downregulation of severalmembers of the plakin family including periplakin (PPL), envoplakin (EVPL), and involucrin(IVL) that are essential for terminal differentiation of keratinocytes. MRM and Western blotanalysis confirmed differential expression of several candidate proteins. Our study providesinsights into molecular alterations upon chronic arsenic exposure on skin.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/2667
    Subjects: Molecular & Human Genetics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 07 Jun 2017 12:03
    Last Modified: 07 Jun 2017 12:20
    Official URL: http://dx.doi.org/10.1002/pmic.201600257
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