Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT1_TP_R2.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT1_TP_R1.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/24_reports_prot.xml.prot.xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_08_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_09_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_02_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_04_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_06_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_05_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_07_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_10_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_11_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_12_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_03_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_09_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT1_TP_01_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT1_TP_01_R2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_07_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_08_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_04_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_05_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_06_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_03_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_12_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_11_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_10_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/HaCaT_TP_02_R1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/01/PXD001645/24_reports_pep.xml.pep.xmlprimaryOK200003870pandey@jhmi.eduAkhilesh PandeyMass SpectrometryShotgun proteomicsNot availableToxicityHacatSodium arsenitehttp://www.ebi.ac.uk/pride/archive/projects/PXD001645KeratinocyteSkinHacat CellHaCaT cells treated with 100nM arsenic were maintained in DMEM containing lysine and arginine (12C6-arginine and 12C6-lysine) supplemented with 5% FBS, 2 mM L-glutamine, 100 U/mL penicillin and 100 μg/mL streptomycin. For SILAC adaptation the parental cells were maintained in custom made DMEM without lysine and arginine and supplemented with heavy stable isotopic forms of lysine and arginine (13C6 L-lysine and 13C6 L-arginine). Arsenic treatment was withdrawn for 24 hours prior to any experiment. Both parental and arsenic treated HaCaT cells were grown to 80% confluency for harvesting. The cells were washed with cold PBS lysed in lysis buffer (20 mM HEPES pH8.0, 9 M urea, 1 mM sodium orthovanadate, 2.5 mM sodium pyrophosphate, 1 mM β-glycerophosphate), sonicated and centrifuged at 16,000 × g at 15 °C for 20 min. Protein estimation was carried out by using BCA assay. Equal amounts of protein were mixed in a ratio of 1:1. This protein mix was subjected to trypsin digestion. The pooled lysates were reduced and alkylated followed by trypsin digestion. The peptide sample was cleaned using Sep-Pak C18 cartridges (Waters, Milford, MA, USA) and lyophilized. The lyophilized peptides were subjected to basic pH reverse phase liquid chromatography. The peptides were fractionated on 1290 infinity HPLC system (Agilent, Santa Clara, CA,USA) . A total of 90 fractions were collected, concatenated to 12 fractions and dried using speedvac for LC-MS analysis on the LTQ Orbitrap Velos mass spectrometer interfaced with Easy nLC II (Thermo Scientific, Bremen, Germany).PrideSILACiodoacetamide derivatized residue6x(13)C labeled residuemonohydroxylated residueProteome Discoverer 1.4 (Version 1.4.0.288) (Thermo Fisher Scientific, Bremen, Germany) was used for peak list generation and database searches. Precursor mass range of 350–8000 Da and signal to noise ratio of 1.5 were the criteria used for generation of peak lists. Sequest and Mascot search algorithms were used for database searches with NCBI RefSeq 59 as reference database (containing common contaminants). Oxidation of methionine and SILAC 2-plex (13C6 L-lysine and 13C6 L-arginine) were used as dynamic modifications. Carbamidomethylation of cysteine residue was used as static modification. A maximum of one missed cleavage was allowed for tryptic peptides. Mass error window of 10 ppm and 0.1 Da were allowed for precursors and fragments, respectively. Decoy database was used to calculate false discovery rate (FDR) with a cut-off of 1%.ProteomicsAkhilesh PandeyLTQ Orbitrap VelosPARTIALMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, 21205, USAHomo Sapiens (human)pandey.akhilesh@mayo.edu28000977 Mir SA, Pinto SM, Paul S, Raja R, Nanjappa V, Syed N, Advani J, Renuse S, Sahasrabuddhe NA, Prasad TS, Giri AK, Gowda H, Chatterjee A. SILAC-based quantitative proteomic analysis reveals widespread molecular alterations in human skin keratinocytes upon chronic arsenic exposure. Proteomics. 2016 Oct 19 10.1002/pmic.201600257BiomedicalDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905United StatesChronic exposure to arsenic is associated with dermatological and nondermatological disorders. Consumption of arsenic-contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs, and gastrointestinal tract. Although arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues including skin. Epidemiological studies suggest the association of skin cancer upon arsenic exposure, however, the mechanism of arsenic-induced carcinogenesis is not completely understood. We developed a cell line based model to understand the molecular mechanisms involved in arsenic-mediated toxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT, was chronically exposed to 100 nM sodium arsenite over a period of 6 months. We observed an increase in basal ROS levels in arsenic-exposed cells. SILAC-based quantitative proteomics approach resulted in identification of 2111 proteins of which 42 proteins were found to be overexpressed and 54 downregulated (twofold) upon chronic arsenic exposure. Our analysis revealed arsenic-induced overexpression of aldo-keto reductase family 1 member C2 (AKR1C2), aldo-keto reductase family 1 member C3 (AKR1C3), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) among others. We observed downregulation of several members of the plakin family including periplakin (PPL), envoplakin (EVPL), and involucrin (IVL) that are essential for terminal differentiation of keratinocytes. MRM and Western blot analysis confirmed differential expression of several candidate proteins. Our study provides insights into molecular alterations upon chronic arsenic exposure on skin.SILAC-based quantitative proteomic analysis reveals widespread molecular alterations in human skin keratinocytes upon chronic arsenic exposure.Mir Sartaj Ahmad SA, Pinto Sneha M SM, Paul Somnath S, Raja Remya R, Nanjappa Vishalakshi V, Syed Nazia N, Advani Jayshree J, Renuse Santosh S, Sahasrabuddhe Nandini A NA, Prasad T S Keshava TS, Giri Ashok K AK, Gowda Harsha H, Chatterjee Aditi AForms, arsenicum, Lysine Hydrochloride, chronic obstructive pulmonary disease (COPD), Basodexan, Bca, dmTAF[[II]]230, Polypeptides, protein polypeptide chains, Lysine Acetate, L-glutamine, T22F8_160, ATGPR7, Chronic irreversible airway obstruction, Urea, 2, L-2-aminoglutaramic acid, GRP8, GRP7, AGM4, Sodium Ion, L Lysine, O-2-deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5-deoxy-3-C-formyl-alpha-L-lyxofuranosyl-(1-4)-N, bca, (S)-2-amino-5-guanidinopentanoic acid, TFIID TAF250, sarcoma of breast, cel, K, N'-bis(aminoiminomethyl)-, 32P2-labeled cpd, Q, Salt, As, R, Arginine, CAFL - Chronic airflow limitation, Monohydrate DL-Arginine Acetate, proteins, HPLC, AI047805, Strepto-Hefa, decreased, LYS, disease (COPD), scientific observation, Lysin, sample, autolysin activity, dTAF[[II]]230, chronic obstructive lung disease [Ambiguous], BZRP, Liquid Chromatography, TAF200, arginine, Penicillin, breast sarcoma, PBS, PBR, CHRONIC OBSTRUCTIVE AIRWAY DIS, Dm1, arsenic, sodium, Streptomycine Panpharma, Bickel-Fanconi glycogenosis, Airflow Obstruction, natrium, Estreptomicina Normon, GLYCINE-RICH PROTEIN 8, Chronic Obstructive Airways Disease, glycogenosis due to GLUT2 deficiency, Chronic obstructive lung disease, glycogen storage disease due to GLUT2 deficiency, LY57, glycogenosis Fanconi EXACT, proportionality, pooled, rate, alpha, (S)-2, beta Trypsin, Painful bladder syndrome, F2G1.4, Taf250, Thermo Scientific., OBSTRUCTIVE PULMONARY DISEASE (COPD), bacteriolytic toxin activity, arsenico, GSD type XI, TAF230, BPBS, GLUTAMINE, sarcoma of the breast, Streptomycin Grünenthal, CAO - Chronic airflow obstruction, Levoglutamide, high weight, Strepto Fatol, Carbamide, CHRONIC OBSTRUCTIVE PULM DIS, Chronic obstructive pulmonary disease NOS, protein-containing complex, body system, and RNA binding 1, CG7826, Chronic obstructive pulmonary disease finding, Ion Level, PULMONARY DISEASE (COPD), Ly57, heavy, CG7835, CG42273, system, Lysine, Fanconi Bickel syndrome, Carmol, proportion, anatomical systems, dTAF[[II]]250, cell, (2S)-2, hepatic glycogenosis with Fanconi nephropathy, Monosodium Salt, beta-Trypsin, pk18, study assay, MBR, dTAF250, Sep-Pak C18, ATGRP7, ATGRP8, NEC, L-Arg, PTBR, Chronic, peptidos, Antibiotics, 4-(2-hydroxyethyl)-, measuring, decahydrate, chronic obstructive airways disease NOS, Fanconi-Bickel disease, COAD, BG:DS00004.13, anhydrous sodium pyrophosphate, L-Isomer, COLD - Chronic obstructive lung disease, buffer, Cell, chronic, dTAF230, Arsen, polypeptide, tetrasodium salt, Experiment, Temperatures, native protein, L-Isomer Arginine, carbonyldiamide, Acetate, chemical analysis, TAF[[II]]250/230, Glutamic acid 5-amide, Sodium, MIXL, (COPD), chronic airway obstruction, chronic obstructive, L-Lysine, glycogenosis, CAL - Chronic airflow limitation, U/ml, Sodium Ion Level, Taf[[II]]250, AU020952, holin, Glutamic acid amide, underdeveloped, (2S)-2-amino-5-guanidinopentanoic acid, GR-RBP7, GR-RBP8, Na, Natrium, mDRC, ME-IV, hepatorenal glycogenosis with renal fanconi syndrome, chronic obstructive lung disease (disorder), quotient, Sodium 23, Enisyl, chronic obstructive pulmonary disease, T22F8.160, Fanconi syndrome with intestinal malabsorption and galactose intolerance, determination, and rna binding 2, L-arginine, DL-Arginine Acetate, Chronic Airflow Obstructions, Monohydrate, HEPES Monosodium Salt, protein, lysis, L-(+)-glutamine, sodium diphosphate, peptide, sodio, L-Glutaminsaeure-5-amid, Streptomycin Sulfate, ClvPrd, peptido, chronic obstructive airways disease NOS (disorder), Min, GSD due to GLUT2 deficiency, Arg, Chronic Obstructive Pulmonary Disease (COPD), protein aggregate, present in fewer numbers in organism, DmelCG42273, MIX, Penicillin Antibiotics, HEPES Monosodium, COLD (chronic obstructive lung disease), peptides, NEC in ICD9CM_2006, E927b, (S)-2-Amino-5-guanidinovaleric acid, hypoplasia, epsilon-diaminocaproic acid, min, mAPC, IBP, Chronic airflow limitation, 1-Piperazineethanesulfonic acid, GLYCINE RICH PROTEIN 7, necrosis, Lyw-57, Bladder pain syndrome, glycine-rich RNA-binding protein 8, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, L-Arginin, ratio, CHRONIC, obstructive lung disease, Arginine Hydrochloride, Dmel_CG7826, TAFII-250, TAF250/230, glycogen storage disease 11, Airflow Obstructions, ur, pulmonary disease (COPD), SLP65, any method, carbamide, Sodium-23, Ly-57, TAFII250, 33As, Streptomycin Sulphate, low temperature, CHRONIC OBSTRUCTIVE, chronic obstructive pulmonary disease and allied conditions, lysine, Chronic airway disease, bacteriocin activity, NOS, Dmel_CG7835, COPD NOS, L-Arginine, CHRONIC OBSTRUCTIVE LUNG DIS, Mnb, MNB, Chronic airway obstruction, MILD1, SLP-65, Painful Bladder Syndrome, cold, BASH, DMEM, AW124434, CG17603, TAF[[II]], Fanconi-Bickel syndrome, L-glutamic acid gamma-amide, organ system, Chronic Airflow Obstruction, H2NC(O)NH2, lysin activity, hepatic glycogenosis with amino aciduria and glucosuria, SR3-5, COPD - Chronic obstructive pulmonary disease, chronic obstructive airways disease, Polypeptide, Fanconi type, obstructive pulmonary disease (COPD), HEPES, COLD, chronic obstructive lung disease, 1728, Bladder Pain Syndrome, GLUT2 deficiency, d230, 5-diamino-5-oxopentanoic acid, DISEASE (COPD), L Isomer, dTAFII250, FBS, Fbs, circadian rhythm, (2S)-2-amino-4-carbamoylbutanoic acid, EfW1, Arsenic-75, L-(+)-arginine, Buffer, Karbamid, Cold, Pulmonary Disease, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, polypeptide chain, reduced, dmTAF1, Strepto-Fatol, Taf230, subnumerary, Harnstoff, Strepto Hefa, tiny, Level, pseudo-phlorizin diabetes, TAF250, Taf200, Arsenic, Cold Temperatures, D-Streptamine, diphosphoric acid, Taf1p, decreased number, Chronic Obstructive, Estreptomicina CEPA, glycogen storage disease type 11, L-Glutamine, N-2-Hydroxyethylpiperazine-N'-2'-ethanesulfonic Acid, TAF, BLNK-S, D-MEM, COPD, disodium pyrophosphate, small, COAD - Chronic obstructive airways disease, DYRK1, TAF[[II]]250, DBI, protein complex, not elsewhere classified, l(3)84Ab, L-2-Aminoglutaramic acid, DL Arginine Acetate, PULM DIS CHRONIC OBSTRUCTIVE, Peptide, Chronic obstructive pulmonary disease finding (finding), PKBS, natural protein, p230, glycogen storage disease XI, Protein, Hydrochloride, TFIID, L Arginine, Dyrk1, L-Glutamin, GLYCINE-RICH RNA-BINDING PROTEIN 7, connected anatomical system, glycogen storage disease type XI, tetrasodium pyrophosphate, chronic obstructive airway disease, Temperature, hepatorenal glycogenosis with renal Fanconi syndrome, TAF[[II]]230, GSD type 11, Streptomycin Sulfate (2:3) Salt, uree, Dops, urea, CC1, Tripcellim, N 2 Hydroxyethylpiperazine N' 2' ethanesulfonic Acid, TAF[II]250, FBS1, Fbs1, Arsenic 75, sample population, UREA, Trypure, trisodium pyrophosphate, 11Na, DmelCG17603, Estreptomicina Clariana, cold (chronic obstructive lung disease), Peptid, Chronic Obstructive Lung Disease, assay, 6-diaminohexanoic acid, TAF1dermis plus epidermis plus hypodermis, the integument, arsenicum, region of skin, human being, Oct-11a, pelt, Otf-11, Skn-li, number, skin zone, slow time, integumental organ, increased time, presence, chronic, epidermis, Arsenic-75, Arsen, count in organism, skin plus hypodermis, 33As, skin region, Oct11, increased period, arsenic, BC033609, proteomic analysis, high time, Skin-1a, prolonged period, tegument, Skin, integumentum commune, Skn-1a, Arsenic 75., Arsenic, skin, vertebrate integument, dermoid system, As, entire skin, Keratinocyte, man, SKIN, human, mKIAA0493, Epoc-1, portion of skin, skin organ, vertebrate epidermis, integument, Otf11, Fam91a1, Chronic, arsenico, quantitative, entire integument, dermal system, AV220772, skin and subcutaneous tissue, presence or absence in organismNoise, 2-amino-4-(methylsulfanyl)butanoic acid, l(1)VE614, AW549739, DL-Methionine, False, L-arginine, T5E21.12, 2-Amino-4-(methylthio)butyric acid, Ct, Pollution, L Isomer, cleavage, FBN, arginine, precursor, L-Isomer, Peptide, ACMICD, L-(+)-arginine, polypeptide, peptide, Polypeptides, Cut, L-Isomer Methionine, Methionine, peptido, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, l(1)7Ba, ECTOL1, l(1)7Bb, Algorithm, L-Methionine, CG11387., MFS1, Methionin, methionine, Hmet, Arg, BcDNA:GH10590, WMS, Pedameth, Data Base, WMS2, Met, T5E21_12, C79691, parent ion, L-Arginine, proportion, (S)-2-amino-5-guanidinopentanoic acid, F, peptides, M, (S)-2-Amino-5-guanidinovaleric acid, (2S)-2-amino-5-guanidinopentanoic acid, proportionality, R, common, rate, MASCOT, MASS, kf, Noises, OCTD, Lccp, incised, mKIAA0989, 2-amino-4-(methylthio)butanoic acid, precursor ion, 10^[-6], DmelCG11387, ppm, SSKS, quotient, alpha-amino-gamma-methylmercaptobutyric acid, L-Arg, CT, Peptid, peptidos, Noise Pollution, Polypeptide, GPHYSD2, metionina, Racemethionine, Liquimeth, SGS, ratio, L-ArgininWater, the integument, arsenicum, pelt, Skn-li, Ass-1, "skin cancer" EXACT [CSP2005:2020-0536], "malignant neoplasm of skin NOS (disorder)" EXACT [SNOMEDCT_2005_07_31:188143008], Na(+)n-(-As(O(-))O-)-n, malignant zone of skin neoplasm, Cancer of Skin, tumor of zone of skin, catena-poly[(oxidoarsenate-mu-oxido)]sodium, cancer of skin, dmTAF[[II]]230, malignant tumour of skin, diseases, Associations, AA408052, pulmones, zone of skin cancer, Line, fold, diseases and disorders, lungs pair, integumentum commune, Epidemiologic Study, human disease, sodium metaarsenite, TFIID TAF250, cel, Tissue, As, alimentary tract, dermoid system, iecur, entire skin, Oncogeneses, proteins, skin tumour, c-ros-1, Bottled, ASS, Otf11, Fam91a1, Homo sapiens disease, associated, alimentary system, AV220772, Cancer of the Skin, skin and subcutaneous tissue, GI Tracts, dTAF[[II]]230, malignant neoplasm of skin, Epidemiologic, CA - skin cancer, TAF200, "malignant neoplasm of skin, integumental organ, (NaAsO2)n, Epidemiological Studies, TAFII-250, TAF250/230, KML001, results, Potable Water, malignant tumor of skin, 33As, TAFII250, increased period, arsenic, BC033609, margin of safety, tumor of skin, "melanoma and Non-melanoma skin cancer" EXACT [NCI2004_11_17:C2920], Digestive Tract, Lines, gastrointestinal tract, melanoma and non-melanoma skin cancer, Digestive Tracts, skin neoplasm, Skin Cancer, pooled, lien, malignant tumour of the skin, exposed, CG17603, GI tract, TAF[[II]], human, mKIAA0493, disease, Potable, Kidneys, vertebrate epidermis, MCF3, Oncogenesis, Taf250, gastrointestinal system, SR3-5, arsenico, Gastrointestinal Tracts, entire integument, dermal system, melanoma and Non-melanoma skin cancer, malignant skin neoplasm, GI Tract, TAF230, gastrointestinal (GI) tract, skin cancer, dermis plus epidermis plus hypodermis, other disease, d230, region of skin, Tumorigeneses, human being, Peptidomics, Otf-11, skin neoplasms, Neoplasms, sodium meta-arsenite, number, Gene, dTAFII250, slow time, neoplasm of skin, EfW1, presence, epidermis, Arsenic-75, jecur, neoplasm of skin by site, dmTAF1, Taf230, Studies, Gene Products, disease or disorder, malignant skin tumor, Skn-1a, TAF250, study, Arsenic, Taf200, dTAF[[II]]250, skin, "malignant neoplasm of skin (disorder)" EXACT [SNOMEDCT_2005_07_31:372130007], malignant tumor of the skin, cell, Taf1p, tumour of the skin, Sodium dioxoarsenate, KC, gastroenterological system, SKIN, man, non-neoplastic, Study, gastro-intestinal system, dTAF250, skin organ, extruding from, zone of skin tumor, cancer of the skin, Chronic, disorder, zone of skin tumour, toxic potential, Skin Neoplasm, cancer of zone of skin, NaAsO2, TAF, Bottled Water, Epidemiological, Cancer, malignant skin tumour, malignant neoplasm of the skin, TAF[[II]]250, Oct-11a, malignant, exits through, Proteins, disorders, "malignant neoplasm of skin" EXACT [MTH:NOCODE], Cell Lines, skin zone, l(3)84Ab, medical condition, BG:DS00004.13, lungs, skin tumor, increased time, Tumorigenesis, Sodium arsenite, chronic, Cell, dTAF230, Arsen, skin plus hypodermis, count in organism, skin region, Oct11, Drinking, p230, Protein, high time, Neoplasm, Skin Cancers, zone of skin neoplasm (disease), TAF[[II]]250/230, condition, TFIID, Epidemiological Study, prolonged period, Skin-1a, ROS, tegument, Skin, malignant neoplasm of zone of skin, skin benign neoplasm, Taf[[II]]250, neoplasm of the skin, "CA - skin cancer" EXACT [SNOMEDCT_2005_07_31:363511009], TAF[[II]]230, zone of skin neoplasm, Carcinogeneses, vertebrate integument, TAF[II]250, Cancers, set of lungs, Skn-1a., Arsenic 75, Epoc-1, tumor of the skin, Protein Gene Products, Livers, tumour of zone of skin, Gene Proteins, portion of skin, unspecified (disorder)" EXACT [SNOMEDCT_2005_07_31:190107001], DmelCG17603, integument, Lungs, neoplasm of zone of skin, quantitative, Including melanoma, tumour of skin, TAF1, presence or absence in organismWater, tweenase activity, arsenicum, Kinship, srxy8, "malignant neoplasm of skin NOS (disorder)" EXACT [SNOMEDCT_2005_07_31:188143008], malignant zone of skin neoplasm, CG18436, hluPGFS, catena-poly[(oxidoarsenate-mu-oxido)]sodium, 10-dimethyl-3-(1-methylethyl)-11-oxabicyclo(8.1.0)undec-6-en-2-yl ester, dmTAF[[II]]230, malignant tumour of skin, triacylglycerol lipase activity, Associations, pulmones, GLCL, Line, HAKRD, benzoquinone, 1, 2, Life Cycle, 3, 4, HAKRB, triolein hydrolase activity, oxidoreductase activity, integumentum commune, Epidemiologic Study, NAD(P)H:quinone oxidoreductase activity, Kinship Network, TFIID TAF250, cel, triglyceride hydrolase activity, HAKRe, CG1540, Tissue, As, alimentary tract, MCDR2, entire skin, proteins, skin tumour, c-ros-1, Bottled, tweenesterase activity, Ligase, Glutamylcysteine, amno N-AP, Otf11, Fam91a1, Homo sapiens disease, NAD(P)H dehydrogenase, alimentary system, amano AP, AV220772, Cancer of the Skin, skin and subcutaneous tissue, DD, quinone reductase activity, dTAF[[II]]230, Glutamate Cysteine Ligase, malignant neoplasm of skin, TAF200, AKR1C-pseudo, "malignant neoplasm of skin, (NaAsO2)n, Epidemiological Studies, Potable Water, Dihydrodiol Dehydrogenase-Bile Acid Binding Protein, NAD(P)H(2) dehydrogenase (quinone) activity, increased period, arsenic, amano CE, margin of safety, tumor of skin, "melanoma and Non-melanoma skin cancer" EXACT [NCI2004_11_17:C2920], Digestive Tract, IVL, melanoma and non-melanoma skin cancer, NMORI, skin neoplasm, takedo 1969-4-9, BABP, pooled, malignant tumour of the skin, exposed, human, NMOR1, babp, menadione oxidoreductase activity, p-benzoquinone, MCF3, Taf250, gastrointestinal system, arsenico, AKR1C2 Protein, entire integument, GI Tract, viologen accepting pyridine nucleotide oxidoreductase activity, TAF230, Benzoic acid, skin cancer, region of skin, CT41988, Peptidomics, Otf-11, Neoplasms, sodium meta-arsenite, number, terminal differentiation, tributyrase activity, jecur, PGFS, period, NAD(P)H-quinone dehydrogenase activity, flavoprotein NAD(P)H-quinone reductase activity, Gene Products, disease or disorder, Glutamate-Cysteine, HA1753, 5-cyclohexadiene-1, Skn-1a, dTAF[[II]]250, skin, "malignant neoplasm of skin (disorder)" EXACT [SNOMEDCT_2005_07_31:372130007], malignant tumor of the skin, cell, reduced NAD(P)H dehydrogenase activity, post-heparin plasma protamine-resistant lipase, KC, SKIN, man, giant cell carcinoma of the lung, Study, gastro-intestinal system, dTAF250, skin organ, ddh2, extruding from, zone of skin tumor, capalase L, giant cell lung carcinoma, Naphthoquinone reductase activity, Chronic, DDH2, Skin Neoplasm, DT-diaphorase activity, NAD(P)H menadione reductase activity, Cancer, malignant skin tumour, malignant neoplasm of the skin, Oct-11a, Glutamylcysteine Synthetase, DHQU, Family Research, AW553870, salt-resistant post-heparin lipase, Proteins, disorders, skin zone, BG:DS00004.13, lungs, skin tumor, vitamin K reductase activity, increased time, Sodium arsenite, chronic, Cell, dTAF230, menadione reductase activity, Family Members, Arsen, hakrd, skin plus hypodermis, hepatic lipase, 4-dione, chemical analysis, high time, Neoplasm, TAF[[II]]250/230, condition, Epidemiological Study, vitamin-K reductase activity, DTD, ROS, liver lipase, Dihydrodiol Dehydrogenase 2, Skin, Dihydrodiol Dehydrogenase 3, malignant neoplasm of zone of skin, skin benign neoplasm, Taf[[II]]250, neoplasm of the skin, other acceptor, SRM, Carcinogeneses, azoreductase activity, triglyceridase activity, NAD(P)H dehydrogenase activity, Cancers, set of lungs, Skn-1a., giant cell carcinoma, Keratinocyte, Epoc-1, NAD(P)H-quinone oxidoreductase activity, CG33103, Gene Proteins, para-benzoquinone, Families, Glclc, reduced nicotinamide adenine dinucleotide (phosphate, quantitative, GLCLC, Relatives, Networks, the integument, akr1c2, pelt, naphthoquinone reductase activity, determination, Skn-li, "skin cancer" EXACT [CSP2005:2020-0536], Na(+)n-(-As(O(-))O-)-n, Cancer of Skin, tumor of zone of skin, amano B, mcdr2, SRXY8, amano P, cancer of skin, D9Wsu168e, diseases, zone of skin cancer, QR1, AKR1C3 Protein, diseases and disorders, lungs pair, DD-2, Family Life Cycle, human disease, sodium metaarsenite, EVPK, PPL, NAD(P)H2 dehydrogenase (quinone), dermoid system, iecur, Oncogeneses, glycerol-ester hydrolase activity, TAG activity, NSC36324, triacetinase activity, meito sangyo OF lipase, ppl, ppn, p-benzoquinone reductase activity, associated, Family Life Cycles, GI Tracts, acting on NADH or NADPH, Epidemiologic, CA - skin cancer, integumental organ, lipazin, TAFII-250, TAF250/230, heparin releasable hepatic lipase, KML001, results, Multiple Reaction Monitoring, malignant tumor of skin, 33As, TAFII250, gamma Glutamyl Cysteine Synthetase, gamma-Glutamyl-Cysteine, hbab, amano CES, BC033609, Filiation, HBAB, Lines, CT3186, gastrointestinal tract, Digestive Tracts, HSD17B5, 5-trimethoxy-, dehydrogenase, tributyrinase activity, Skin Cancer, lien, CG17603, 4-(acetyloxy)-6, GI tract, TAF[[II]], NAD(P)H:(quinone-acceptor)oxidoreductase activity, mKIAA0493, NQO1, Life Cycles, disease, Potable, Kidneys, vertebrate epidermis, Oncogenesis, DD|BABP, SR3-5, diaphorase activity, GCL, DmelCG33103, NAD(P)H: menadione oxidoreductase activity, Gastrointestinal Tracts, GCS, reduced nicotinamide-adenine dinucleotide (phosphate) dehydrogenase activity, triacylglycerol ester hydrolase activity, dermal system, melanoma and Non-melanoma skin cancer, steapsin, malignant skin neoplasm, time, gastrointestinal (GI) tract, dermis plus epidermis plus hypodermis, other disease, d230, Tumorigeneses, human being, 17-beta-Hydroxysteroid Dehydrogenase Type 5, Family Member, skin neoplasms, Gene, dTAFII250, slow time, 4-benzoquinone, Network, neoplasm of skin, EfW1, presence, epidermis, Arsenic-75, Dihydrodiol Dehydrogenase Bile Acid Binding Protein, neoplasm of skin by site, dmTAF1, Taf230, GEH, tween hydrolase activity, Studies, butyrinase activity, malignant skin tumor, cacordase activity, TAF250, GLCL-H, lung giant cell carcinoma, study, Arsenic, Taf200, MRM, Research, gamma-Glutamyl-Cysteine Synthetase, tributyrin esterase activity, Taf1p, tumour of the skin, Sodium dioxoarsenate, gastroenterological system, non-neoplastic, cancer of the skin, disorder, GCLC, zone of skin tumour, toxic potential, meito MY 30, Kinship Networks, cancer of zone of skin, NaAsO2, TAF, Dia4, DIA4, Aldo Keto Reductase Family 1 Member C3, Family, Aldo Keto Reductase Family 1 Member C2, Bottled Water, Epidemiological, TAF[[II]]250, phylloquinone reductase activity, tween-hydrolyzing esterase activity, triacylglycerol acylhydrolase activity, malignant, exits through, quinone) activity, "malignant neoplasm of skin" EXACT [MTH:NOCODE], Cell Lines, l(3)84Ab, medical condition, NADH-menadione reductase activity, Tumorigenesis, hepatic monoacylglycerol acyltransferase, GA 56, count in organism, skin region, Oct11, Drinking, p230, Protein, Skin Cancers, zone of skin neoplasm (disease), Synthetase, TFIID, DD3, dd2, DD2, prolonged period, Skin-1a, tegument, "CA - skin cancer" EXACT [SNOMEDCT_2005_07_31:363511009], TAF[[II]]230, zone of skin neoplasm, Ggcs-hs, NSC-36324, vertebrate integument, TDD, TAF[II]250, DDX, Arsenic 75, glycerol ester hydrolase activity, tumor of the skin, Protein Gene Products, Livers, tumour of zone of skin, portion of skin, unspecified (disorder)" EXACT [SNOMEDCT_2005_07_31:190107001], L-Glutamate:L-cysteine gamma-ligase (ADP-forming), DmelCG17603, integument, Lungs, assay, neoplasm of zone of skin, giant cell carcinoma of lung, Including melanoma, tumour of skin, TAF1, presence or absence in organism, 17 beta Hydroxysteroid Dehydrogenase Type 5dermis plus epidermis plus hypodermis, the integument, arsenicum, region of skin, human being, Oct-11a, pelt, Otf-11, Skn-li, number, skin zone, slow time, integumental organ, increased time, presence, chronic, epidermis, Arsenic-75, Arsen, count in organism, skin plus hypodermis, 33As, skin region, Oct11, increased period, arsenic, BC033609, proteomic analysis, high time, Skin-1a, prolonged period, tegument, Skin, integumentum commune, Skn-1a, Arsenic 75., Arsenic, skin, vertebrate integument, dermoid system, As, entire skin, Keratinocyte, man, SKIN, human, mKIAA0493, Epoc-1, portion of skin, skin organ, vertebrate epidermis, integument, Otf11, Fam91a1, Chronic, arsenico, quantitative, entire integument, dermal system, AV220772, skin and subcutaneous tissue, presence or absence in organism387trueSILAC-based quantitative proteomic analysis reveals molecular alterations in human skin keratinocytes upon chronic exposure to arsenicChronic exposure to arsenic is associated with dermatological and non-dermatological disorders. Consumption of arsenic contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs and gastrointestinal tract. Although, arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues such as skin. Epidemiological studies on arsenic suggest the association of skin cancer upon arsenic exposure, however, the exact mechanism of arsenic induced carcinogenesis is not completely understood. We have developed a cell line-based model to understand the molecular mechanisms involved in arsenic mediated toxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT was exposed to 100nM sodium arsenite for six months. We observed an increase in the basal ROS levels in arsenic exposed cells along with the increase in anti-apoptotic proteins. SILAC-based quantitative proteomics approach resulted in the identification and quantitation of 2,181 proteins of which 39 proteins were found to be overexpressed (≥2-fold) and 56 downregulated (≤2-fold) upon chronic arsenic exposure. Our study provides comprehensive insights into the molecular basis of chronic arsenic exposure on skin.2017-01-022015-01-05PXD00164528065516460991804982953585111454224942024527872842188090368093270429330845811363336351524260119834300662758385NCBITaxon:128068888561896111430118726355557114526236493461364031952065126957366649274670738538836411354615821582310665688954762721123294422291180992323122586365458333460792519365914320597129386558195851149315242592637371250232NCBITaxon:127211195774818661488584310430024513586722175543740816918045426683429531945305861266835149822505814963674452158554528113208147956410039237514636942049433208964208963445974137979138712728384400667453293529367156759388036478434716052165994048321659721659545501315282693042165915627161696833218321729204277944762376454317203094980197525556978159509439843948840479NCBITaxon:2157525338551531051067439899037122857759515205968762262311210884555588845587077918178081736309431794571698936160488409859NCBITaxon:37162104782679401505907148364320421061320491381693630355543204663263331199456545351102541110321745921612926420128867641002642036945694101676341021076127735152486713165823925472793342814613584301417298760917463345774449167547604893212873567568403013506219172651813019411192943936711041131023932025559863258278839659104759347495109716049016529983552566317585439801102432608663102459808757417555183201964471452680457966313670190832331156114155355104219325552113834397634981812359871069955529NCBITaxon:4751850298335476113615741465477180066556484337677299767982510216998238976484074137351155711089725482444474153NCBITaxon:50557899698441000364653493341471474935480194675129911435974127647313708632654787656589363983532215958936698381920111067757727103481985234878026555447946409860995861571871766859919157295137221171101292921076878349741986020280914884063342492342351523359859886559746499870392021110729433117113936352721598741908503711708271170828418235024145113969293190219782247463604614712374940237593972328758172253256648905079452659600131972211915853101774208588596NCBITaxon:615750521028307989515586411051989972375059576131720002634196102641088878176179212190659407121906772275885815689964975151950582873757244NCBITaxon:22023717NCBITaxon:17036122019998570506050617476792745062724915961533355418400524643213686150596487844612286662941786661347515363291018194301086731018510184NCBITaxon:1763573039635586331492862876705801321650852718481865368595105135553482260710185687294296110091416333NCBITaxon:619184023210007348824123363630710470058127187878645159812894555663577553470951451225786425011449447260704NCBITaxon:13356262607052607076584574054163677483167233150561007133705654195NCBITaxon:305550445791399878168119011928752829126806315327341478281055524NCBITaxon:9606135858469008111167815022830519302836728593008529005NCBITaxon:569382688306401794699151011849943525875913151590144824283811139442258441604193704759272370860423281677285035158199011951953267386370137024924053608838581622488186156227748817562615835583715333760572671193501998086119350216787910857913711371272407190650371475917262981288057125627457572709030903113335503728142433747924910078711082NCBITaxon:96157243359463318586260799141262200298492670NCBITaxon:126371928124921252830385683856959116926610065813735237561275045426662551519788135663837506442233600941293497905463224535247214012575151164990851515143899237453747445446415243235937605920222887051580595536555088157932716029385157811497863389229382894535936479437509173NCBITaxon:68544127542251177529915901090134167387158955210129661030612967158515845158493765939343271591002263767338899046142345128768959119833296646704146479293657616428034116022164133159928038280353690910891768814989462181214108034817939228788929502711313329528282944568617493468191126526997227321890382107601247190400727159736997828114311402064119810871355477436581424507229533796982042321242231291632180334708714537209164573321535815754699287770202060328114319338293550833291292211486437457252649997283035739087183087267271037908550717629970767892683704155737292140532941281607839563924314262654898227377561155962073220865958827355516936053307972551811354914321371597495350261159556143213840607258781414471509493349194963401614334728005936046316461046603815184547448500356709747777195124017484185560133575554792042741580536076994688103762014887100594120037582890931643542826885007123038399001389464940838283594144242322197857742171598921409212205853939621157781154756929793244704749906604162103591905158114452749907312987779913112273170187546991103589915NCBITaxon:37296103609833418710491130798133679531640729946710340157865826453033373306383011306413992530642363650591169654788546981121162034317652616103372861299404458620734011535711195296526117455311147161338654131316634305521323120179836025323731276125523299351299385057316317642619794011513458445772678728623219334151346186208621160791392227983516811961255228149539322323116761757312108077213487999948861856962814084341033517787996321849620994887321392488209711533820961153392095330439375569927612686266447NCBITaxon:2697049339862436941103121958832050920290610130685999758644458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