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Supplementary Table 3. Selected genes in functional groups that are deregulated in liver of zebrafish exposed to arsenic. UniGene Gene (Build 79) Gene Description Difference Mean Log2 (Arsenic vs. Control) symbol *'Early' ** 'Late' ***'Overall' 2.33 Up-Regulated Genes Heat Shock Proteins Dr.11312 heat shock 10kD protein 1 hspe1 2.57 2.09 Dr.7108 heat shock 60kD protein 1 hspd1 4.15 3.14 3.64 Dr.24802 heat shock 70kDa protein 8 hspa8 1.00 2.75 1.87 Dr.20198 heat shock cognate 70-kd protein hsp70 7.04 4.61 5.78 Dr.11431 heat shock protein 4 hspa4 0.81 1.24 1.00 Dr.5588 heat shock protein 4, like hspa4l 3.44 1.41 2.39 Dr.610 heat shock protein 90-alpha hsp90a NS 2.21 1.33 Dr.31066 heat shock protein 90-beta hsp90b 0.88 1.77 1.32 Dr.4503 heat shock protein 9B hspa9b 2.16 3.09 2.79 Antioxidants Dr.9770 peroxiredoxin 3 prdx3 NS 0.84 0.64 Dr.6314 superoxide dismutase 2, mitochondrial sod2 1.79 3.18 2.48 Dr.7977 glutathione peroxidase 1 gpx1 1.55 3.03 2.29 Dr.24921 glutathione peroxidase 4b gpx4b NS 1.68 1.15 Dr.20170 APEX nuclease (multifunctional DNA repair enzyme) 1 1.16 Dr.36769 DNA excision repair protein ERCC-8 Dr.1378 growth arrest and DNA-damage-inducible, beta Dr.33922 replication protein A2 Dr.14857 thyroid autoantigen 70kDa Dr.28707 heme oxygenase 1 hmox1 2.32 NS 1.84 Dr.4829 aminolevulinate, delta-, synthetase 1 alas1 4.53 3.33 3.90 Dr.6496 ferritin, heavy polypeptide 1 fth1 2.52 3.44 2.98 Dr.9052 hypoxia-inducible factor 1 hif1a 0.66 1.48 1.16 Dr.17462 hypoxia up-regulated 1 hyou1 3.72 3.79 3.75 Dr.18233 metallothionein 2 mt2 3.32 3.21 3.26 Dr.7318 proteasome 26S subunit, ATPase 2 psmc2 2.14 NS 1.81 Dr.8213 proteasome subunit, beta type, 9b psmb9b 1.88 1.13 1.47 Dr.20627 proteasome subunit, beta type, 5 psmb5 2.68 NS 2.27 Dr.10596 proteasome subunit, alpha type, 4 psma4 1.64 1.45 1.55 Dr.11843 proteasome subunit, beta type, 6 psmb6 1.20 1.59 1.43 Dr.15038 proteasome subunit, beta type, 1 psmb1 2.02 1.13 1.54 Dr.7957 proteasome subunit, beta type, 8 psmb8 NS 1.96 2.02 Dr.20872 proteasome subunit, alpha type, 6a psma6a NS 1.50 1.42 Dr.20156 proteasome subunit, alpha type, 5 psma5 2.09 1.56 1.93 Dr.19238 cathepsin D ctsd 1.82 2.99 2.40 Dr.26555 cathepsin L, a ctsla 1.20 1.94 1.57 Dr.2951 ubiquinol-cytochrome c reductase core protein II uqcrc2 NS 1.13 0.78 Dr.28845 ubiquitin-activating enzyme E1 ube1 2.35 1.54 1.98 DNA Damage and Repair apex 1.13 1.19 ercc-8 0.48 NS 0.44 gadd45b 1.12 1.70 1.41 rpa2 0.96 1.64 1.46 g22p1 0.58 NS 0.55 Oxidative Stress Inducible Protein Catabolism Dr.9101 ubiquitin-conjugating enzyme E2 variant 2 ube2v2 0.73 0.47 0.60 Dr.25785 ubiquitin-conjugating enzyme E2A (RAD6 homolog) ube2a 0.79 0.78 0.77 Dr.20491 mahogunin, ring finger 1 mgrn1 NS 1.24 0.79 False Discovery Rate (FDR) < 0.5% *'Early' 8h & 24h False Discovery Rate (FDR) < 1% ** 'Late' 48h & 96h False Discovery Rate (FDR) < 5% ***'Overall' 8h to 96h NS Not Significant (FDR > 5%) Supplementary Table 3. (continued page 2) UniGene Gene (Build 79) Gene Description symbol Difference Mean Log2 (Arsenic vs. Control) *'Early' ** 'Late' ***'Overall' Up-Regulated Genes Carbohydrate Catabolism and Energy Dr.11244 glucose phosphate isomerase a gpia 1.91 2.25 2.08 Dr.19225 aldolase a, fructose-bisphosphate aldoa 1.86 2.32 2.06 Dr.20424 transaldolase 1 taldo1 1.76 1.61 1.66 Dr.729 lactate dehydrogenase B4 ldhb 1.36 0.92 1.14 Dr.898 phosphoglycerate kinase 1homolog (human) pgk1 1.37 1.50 1.40 Dr.14669 UDP-glucose dehydrogenase ugdh 2.55 1.12 1.83 Dr.11239 succinate dehydrogenase complex, subunit A sdha 1.11 0.89 1.05 Dr.14189 dihydrodiol dehydrogenase (dimeric), like dhdhl 2.95 1.30 2.12 Dr.10384 NADH dehydrogenase 1, alpha/beta subcomplex, 1 ndufab1 NS 1.82 1.06 Dr.7434 NADH dehydrogenase 1 beta subcomplex, 4 ndufb4 NS 0.73 0.41 Dr.6509 protein disulfide isomerase-related protein pdip5 NS 2.16 1.93 Dr.9457 egl nine homolog 3 (C. elegans) Dr.7906 cytochrome c oxidase subunit VIa polypeptide 1 Dr.4272 ATP synthase, H+ transporting, delta subunit Dr.28209 egln3 2.70 2.30 2.50 coxVIa1 1.19 2.00 1.60 atp5d NS 2.78 3.14 lysyl-tRNA synthetase kars 1.37 2.45 1.93 Dr.20108 glutaminyl-tRNA synthetase qars NS 1.09 1.85 Dr.29078 seryl-tRNA synthetase sars 1.23 1.16 1.16 Dr.1481 valyl-tRNA synthetase 2 vars2 0.43 0.73 0.58 Dr.9798 tyrosyl-tRNA synthetase yars 3.01 2.38 2.69 Dr.1961 ribosomal protein L7-like 1 rpl7l1 2.08 1.22 1.66 Dr.3421 ribosome binding protein 1 homolog (dog) rrbp1 1.55 1.98 1.77 Dr.7787 ribosomal protein S27-like rps27l 2.42 2.12 2.27 Dr.25507 eukaryotic translation initiation factor 2, subunit 2 beta eif2s2 0.98 1.20 1.06 Dr.24841 eukaryotic translation initiation factor 4A, isoform 1A eif4a1a 1.22 NS 0.89 Dr.24582 eukaryotic translation initiation factor 2 subunit 1 alpha like eif2s1l NS 0.80 0.58 Dr.26653 eukaryotic translation initiation factor 2 subunit 3 gamma eif2s3 NS NS 0.67 Dr.1142 dolichyl-diphosphooligosaccharide-protein glycosyltransferase ddost NS 1.67 1.07 Dr.4217 ribophorin II rpn2 NS 2.01 1.19 Dr.445 ribophorin I rpn1 NS 1.95 1.21 Dr.11244 glucose phosphate isomerase a gpia 1.91 2.25 2.08 pc 3.04 4.41 3.73 has2 NS 1.72 1.13 Protein Biosynthesis Glycoprotein and Carbohydrate Biosynthesis Dr.5998 pyruvate carboxylase Dr.10465 hyaluronan synthase 2 Dr.23788 glutathione S-transferase pi gstp1 3.01 3.61 3.31 Dr.16014 glutathione S-transferase omega 1 gsto1 2.67 NS 1.57 Dr.22620 glutathione S-transferase, theta 3 Dr.879 HMT1 hnRNP methyltransferase-like 2 Dr.1867 spermine synthase Dr. 43156 methionine adenosyltransferase 2 alpha Dr.18396 thioredoxin interacting protein Dr.25282 thioredoxin reductase 1 Dr.31444 thioredoxin Dr.18739 thioredoxin-like 1 Arsenic Metabolism False Discovery Rate (FDR) < 0.5% NS gstt3 2.89 4.28 3.58 hrmt1l2 2.33 1.65 2.13 sms 1.00 1.19 1.13 mat2a NS 1.04 0.90 txnip NS 1.46 0.86 txnrd1 2.15 1.73 2.04 tx 3.27 3.58 3.42 txl1 2.51 1.67 2.10 *'Early' 8h & 24h False Discovery Rate (FDR) < 1% ** 'Late' 48h & 96h False Discovery Rate (FDR) < 5% ***'Overall' 8h to 96h Not Significant (FDR > 5%) Supplementary Table 3. (continued page 3) UniGene Gene (Build 79) Gene Description Difference Mean Log2 (Arsenic vs. Control) symbol *'Early' ** 'Late' ***'Overall' Up-Regulated Genes Transportation Dr.1519 RAB6A, member RAS oncogene family rab6a 1.17 0.76 0.97 Dr.7401 RAB5A, member RAS oncogene family rab5a 1.54 1.42 1.56 Dr.4874 RAB1A, member RAS oncogene family rab1a NS 1.45 1.63 Dr.12260 RAB7, member RAS oncogene family rab7 NS 0.42 0.37 Dr.20914 RAB2, member RAS oncogene family rab2 0.70 3.01 1.76 Dr.7872 RAB14, member RAS oncogene family rab14 NS 1.30 0.79 Dr.13128 RAB11A, member RAS oncogene family rab11a 0.96 1.26 1.03 Dr.1915 RAB11B, member RAS oncogene family rab11b 0.68 0.59 0.63 Dr.14855 RAB35, member RAS oncogene family rab35 NS 0.36 0.41 Dr.321 ras-related nuclear protein ran 0.95 0.36 0.65 Dr.2921 coatomer protein complex, subunit alpha copa 0.70 0.83 0.77 1.61 Dr.6631 KDEL endoplasmic reticulum protein retention receptor 2 Dr.12521 translocase of outer mitochondrial membrane 20 kdelr2 0.85 2.54 tomm20 1.07 1.72 Dr.7990 signal recognition particle 54kDa 1.40 srp54 1.11 1.42 1.26 Dr.1209 signal sequence receptor, beta ssr2 NS 0.95 0.81 Dr.297 signal sequence receptor, gamma homolog ssr3 NS 1.39 0.98 Dr.34881 ATP-binding cassette, sub-family C member 4 Dr.10719 ATPase, Na+/K+ transporting, alpha 1a.4 polypeptide Dr.8148 Dr.28281 abcc4 NS 1.62 1.12 atp1a1a.4 1.12 2.45 1.78 catenin alpha ctnna 1.26 1.14 1.24 beta-catenin 2 ctnnb2 NS 0.71 0.52 Cell Adhesion and Cytoskeletal Reorganization Dr.5605 tubulin, beta, 2 tubb2 2.44 2.21 2.32 Dr.28850 tubulin, alpha 8 like tuba8l 3.15 2.61 2.90 Dr.664 tubulin, alpha 8 like 4 tuba8l4 2.85 1.62 2.27 Dr.25213 beta actin 1 bactin1 2.82 1.92 2.34 Dr.1109 beta actin 2 bactin2 NS 1.72 1.10 Dr.1282 keratin 8 krt8 2.00 3.54 2.77 Dr.28198 cofilin 2 like cfl2l NS 1.88 1.35 Dr.28419 profilin 2 like pfn2l 0.85 0.95 0.91 Dr.20954 kinesin 2 kns2 NS 1.53 0.99 Dr.3027 erythrocyte membrane protein band 4.1 (elliptocytosis 1) epb41 0.40 0.29 0.34 0.92 Miscellaneous Dr.8151 signal transduction and activation of transcription 1 stat1 NS 1.14 Dr.275 janus kinase 1 jak1 1.05 1.41 1.23 Dr.4711 ras-related C3 botulinum toxin substrate 1 rac1 1.26 1.36 1.37 Dr.1212 cyclin G1 Dr.25777 mitogen-activated protein kinase-activated protein kinase 2 ccng1 1.15 3.25 2.20 mapkapk2 1.13 NS 0.87 0.91 Dr.4957 myeloid cell leukemia sequence 1a mcl1a 1.00 0.78 Dr.10465 hyaluronan synthase 2 has2 NS 1.72 1.13 Dr.12605 cyclin-dependent kinase inhibitor 1b cdkn1b 0.99873 NS 0.88209 False Discovery Rate (FDR) < 0.5% NS *'Early' 8h & 24h False Discovery Rate (FDR) < 1% ** 'Late' 48h & 96h False Discovery Rate (FDR) < 5% ***'Overall' 8h to 96h Not Significant (FDR > 5%) Supplementary Table 3. (continued page 4) UniGene Gene (Build 79) Gene Description symbol Difference Mean Log2 (Arsenic vs. Control) *'Early' ** 'Late' ***'Overall' Down-Regulated Genes Blood Factors Dr.1565 coagulation factor VII f7 -1.07 NS -0.74 Dr.19652 coagulation factor VIIi f7i -2.50 -2.18 -2.34 Dr.20017 coagulation factor IX f9 -1.64 -1.40 -1.53 Dr.28864 serine (or cysteine) proteinase inhibitor, clade A member 1 serpina1 NS -0.57 -0.43 Dr.4199 serine (or cysteine) proteinase inhibitor, clade C member 1 serpinc1 -1.89 NS -1.27 Dr.356 GATA-binding protein 2 gata2 NS -1.36 -1.46 Dr.10074 platelet-derived growth factor alpha polypeptide pdgfa NS -0.92 -0.95 Dr.26356 hemoglobin alpha embryonic-1 hbae1 NS -0.84 -0.88 Dr.12359 hydroxysteroid 11-beta dehydrogenase 2 hsd11b2 -3.26 -1.60 -2.49 Dr.12949 Deiodinase, iodothyronine, type II dio2 -1.41 -1.49 -1.45 Dr.16113 inhibin, beta A inhba NS -1.50 -1.40 Dr.15260 rev erb beta 2 reverbb2 NS -1.59 -1.27 Dr.32157 Androgen receptor (dihydrotestosterone receptor) ar NS -1.26 -1.07 Dr.11725 Estrogen receptor 2b esr2b NS -1.13 -0.71 Dr.12402 insulin-like growth factor 1 igf1 NS -1.07 -0.68 Dr.583 insulin promoter factor 1 ipf1 -0.73 -0.67 -0.70 Dr.4002 apolipoprotein B apoB -2.63 -1.27 -1.95 Dr.12241 carnitine palmitoyltransferase 1A cpt1A -2.24 -1.49 -1.87 slc27a3 -1.52 -2.21 -1.86 lpl -2.28 NS -1.32 Hormone-related Activity Lipid Metabolism Dr.4342 solute carrier family 27 (fatty acid transporter), member 3 Dr.20185 lipoprotein lipase Dr.6814 fatty acid binding protein 3 fabp3 -0.74 -0.55 -0.65 Dr.3292 monoglyceride lipase mgll -1.42 NS -0.79 Dr.20961 cytosolic phospholipase a2 cpla2 NS -1.28 -0.88 Dr.742 transforming growth factor, beta-induced Dr.563 spondin 2b Dr.31832 Miscellaneous tgfbi -1.33 -1.45 -1.33 spon2b NS -1.90 -1.68 vimentin vim -0.67 -2.17 -1.55 Dr.24216 type I cytokeratin cki -0.72 -1.25 -0.99 Dr.1434 type II cytokeratin ckii NS -0.66 -0.44 Dr.28593 retinol binding protein 1 rbp1 -2.47 NS -2.22 Dr.409 fibroblast growth factor receptor 4 fgfr4 -1.90 -1.46 -1.70 Dr.25162 DNA (cytosine-5-)-methyltransferase 1 dnmt1 NS -0.64 -0.41 Dr.12624 Iroquois homeobox protein 1, b Dr.30528 homeo box D4a Dr.14662 irx1b NS -1.96 -1.96 hoxd4a NS -1.93 -1.89 transcription factor 2, hepatic tcf2 -0.92 NS -0.68 Dr.18290 met proto-oncogene (hepatocyte growth factor receptor) met -0.49 -1.01 -0.75 Dr.608 musculoaponeurotic fibrosarcoma oncogene family, protein B mafb NS -1.29 -1.13 False Discovery Rate (FDR) < 0.5% NS *'Early' 8h & 24h False Discovery Rate (FDR) < 1% ** 'Late' 48h & 96h False Discovery Rate (FDR) < 5% ***'Overall' 8h to 96h Not Significant (FDR > 5%)