iTRAQ-based quantitative proteomic analysis reveals important - - PDF document

iTRAQ-based quantitative proteomic analysis reveals important metabolic pathways for arsenic-induced liver fibrosis in rats Shunhua Wu1*, Jing Li1, Xiang Jin1,2

• 1. Department of Occupational and Environmental health, School of public health,

Xinjiang Medical University, Urumqi, 830011, China

• 2. Shenzhen Omics Medical Research Center, Shenzhen, 518053, China

Running title: proteomic analysis of rat liver under arsenite stress

Supplementary Information Supplementary Table S1. 431 differentially expressed proteins that is common in high dose group and medium dose group than in control group. Supplementary Table S2. KEGG analysis of 431 differentially expressed genes Supplementary Table S3. Gene ontology annotation of the 431 differentially expressed genes. Supplementary Figure S1. Tree-view of the GO enrichment analysis of biological process category for the 171 proteins that decreased in both medium and high dose treatment. Supplementary Figure S2. Tree-view of the GO enrichment analysis of biological process category for the 260 proteins that increased in both medium and high dose treatment. Supplementary Figure S3. Tree-view of the GO enrichment analysis of cellular component category for the 171 proteins that decreased in both medium and high dose treatment. Supplementary Figure S4. Tree-view of the GO enrichment analysis of cellular component category for the 260 proteins that increased in both medium and high dose treatment. Supplementary Figure S5. Tree-view of the GO enrichment analysis of molecular function category for the 260 proteins that increased in both medium and high dose treatment.

GO:0006996

• rganelle organization

GO:0007010 cytoskeleton organization GO:1902589 single-organism organelle

• rganization

GO:0008150 biological_process GO:0009987 cellular process GO:0071840 cellular component

• rganization or

biogenesis GO:0051179 localization GO:0044699 single-organism process GO:0065007 biological regulation GO:0050896 response to stimulus GO:0022610 biological adhesion GO:0032501 multicellular organismal process GO:0050789 regulation of biological process GO:0032502 developmental process GO:0008152 metabolic process GO:0016043 cellular component

• rganization

GO:0044763 single-organism cellular process GO:0051716 cellular response to stimulus GO:0044237 cellular metabolic process GO:0022607 cellular component assembly GO:0043933 macromolecular complex subunit organization GO:0032989 cellular component morphogenesis GO:0007015 actin filament

• rganization

GO:0030030 cell projection

• rganization

GO:0043062 extracellular structure

• rganization

GO:0044085 cellular component biogenesis GO:0030036 actin cytoskeleton

• rganization

GO:0008104 protein localization GO:0034613 cellular protein localization GO:0033036 macromolecule localization GO:0070727 cellular macromolecule localization GO:0051641 cellular localization GO:1902578 single-organism localization GO:0051234 establishment of localization GO:0051649 establishment of localization in cell GO:0098602 single organism cell adhesion GO:0044707 single-multicellular

• rganism process

GO:0044767 single-organism developmental process GO:0044710 single-organism metabolic process GO:0030029 actin filament-based process GO:0048869 cellular developmental process GO:0006928 movement of cell or subcellular component GO:0055086 nucleobase-containing small molecule metabolic process GO:0065008 regulation of biological quality GO:0048519 negative regulation of biological process GO:0050794 regulation of cellular process GO:0032879 regulation of localization GO:0065003 macromolecular complex assembly GO:0070271 protein complex biogenesis GO:0006950 response to stress GO:0042221 response to chemical GO:0006461 protein complex assembly GO:0051259 protein oligomerization GO:0071822 protein complex subunit

• rganization

GO:0033554 cellular response to stress GO:0007155 cell adhesion GO:0098609 cell-cell adhesion GO:0003008 system process GO:0016337 single organismal cell-cell adhesion GO:0034109 homotypic cell-cell adhesion GO:0007275 multicellular organism development GO:0051128 regulation of cellular component organization GO:0031344 regulation of cell projection organization GO:0000902 cell morphogenesis GO:0009653 anatomical structure morphogenesis GO:0048856 anatomical structure development GO:0048468 cell development GO:0007423 sensory organ development GO:0048731 system development GO:0048513 animal organ development GO:0060041 retina development in camera-type eye GO:0030154 cell differentiation GO:0007399 nervous system development GO:0022008 neurogenesis GO:0030182 neuron differentiation GO:0048699 generation of neurons GO:0030198 extracellular matrix

• rganization

GO:0006139 nucleobase-containing compound metabolic process GO:0006165 nucleoside diphosphate phosphorylation GO:0006725 cellular aromatic compound metabolic process GO:0072521 purine-containing compound metabolic process GO:0006753 nucleoside phosphate metabolic process GO:0009117 nucleotide metabolic process GO:0009132 nucleoside diphosphate metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0006793 phosphorus metabolic process GO:0006796 phosphate-containing compound metabolic process GO:0019637

• rganophosphate metabolic

process GO:0016310 phosphorylation GO:0019693 ribose phosphate metabolic process GO:0006807 nitrogen compound metabolic process GO:0034641 cellular nitrogen compound metabolic process GO:1901564

• rganonitrogen compound

metabolic process GO:0044238 primary metabolic process GO:0071704

• rganic substance

metabolic process GO:0046939 nucleotide phosphorylation GO:0006163 purine nucleotide metabolic process GO:0009259 ribonucleotide metabolic process GO:0009135 purine nucleoside diphosphate metabolic process GO:0009185 ribonucleoside diphosphate metabolic process GO:0046483 heterocycle metabolic process GO:0044281 small molecule metabolic process GO:1901657 glycosyl compound metabolic process GO:0009116 nucleoside metabolic process GO:1901360

• rganic cyclic compound

metabolic process GO:1901135 carbohydrate derivative metabolic process GO:0009179 purine ribonucleoside diphosphate metabolic process GO:0046031 ADP metabolic process GO:0009150 purine ribonucleotide metabolic process GO:0009119 ribonucleoside metabolic process GO:0042278 purine nucleoside metabolic process GO:0046128 purine ribonucleoside metabolic process GO:0009126 purine nucleoside monophosphate metabolic process GO:0009161 ribonucleoside monophosphate metabolic process GO:0009167 purine ribonucleoside monophosphate metabolic process GO:0051291 protein heterooligomerization GO:0050877 neurological system process GO:0007600 sensory perception GO:0050953 sensory perception of light stimulus GO:0007601 visual perception GO:0001654 eye development GO:0043010 camera-type eye development

GO:0006082

• rganic acid metabolic

process GO:0043436

• xoacid metabolic process

GO:0016054

• rganic acid catabolic

process GO:1901605 alpha-amino acid metabolic process GO:0016053

• rganic acid biosynthetic

process GO:0006099 tricarboxylic acid cycle GO:0009072 aromatic amino acid family metabolic process GO:0008150 biological_process GO:0008152 metabolic process GO:0009987 cellular process GO:0044699 single-organism process GO:0050896 response to stimulus GO:0050789 regulation of biological process GO:0065007 biological regulation GO:0071840 cellular component

• rganization or

biogenesis GO:0032501 multicellular organismal process GO:0032502 developmental process GO:0044237 cellular metabolic process GO:0044710 single-organism metabolic process GO:0071704

• rganic substance

metabolic process GO:0044238 primary metabolic process GO:0009058 biosynthetic process GO:0009056 catabolic process GO:0006807 nitrogen compound metabolic process GO:0044763 single-organism cellular process GO:0016043 cellular component

• rganization

GO:0044249 cellular biosynthetic process GO:0044255 cellular lipid metabolic process GO:0044248 cellular catabolic process GO:0006575 cellular modified amino acid metabolic process GO:0006725 cellular aromatic compound metabolic process GO:0051186 cofactor metabolic process GO:0034641 cellular nitrogen compound metabolic process GO:0046483 heterocycle metabolic process GO:0006081 cellular aldehyde metabolic process GO:0006793 phosphorus metabolic process GO:0006790 sulfur compound metabolic process GO:0006091 generation of precursor metabolites and energy GO:0044281 small molecule metabolic process GO:0005996 monosaccharide metabolic process GO:0044283 small molecule biosynthetic process GO:0044282 small molecule catabolic process GO:0055086 nucleobase-containing small molecule metabolic process GO:0044707 single-multicellular

• rganism process

GO:0044767 single-organism developmental process GO:0044723 single-organism carbohydrate metabolic process GO:0044711 single-organism biosynthetic process GO:0006629 lipid metabolic process GO:0044712 single-organism catabolic process GO:0055114

• xidation-reduction

process GO:1901657 glycosyl compound metabolic process GO:0019725 cellular homeostasis GO:0015980 energy derivation by

• xidation of organic

compounds GO:0022900 electron transport chain GO:0005975 carbohydrate metabolic process GO:1901576

• rganic substance

biosynthetic process GO:1901575

• rganic substance

catabolic process GO:1901564

• rganonitrogen compound

metabolic process GO:1901360

• rganic cyclic compound

metabolic process GO:0019637

• rganophosphate metabolic

process GO:1901135 carbohydrate derivative metabolic process GO:0035383 thioester metabolic process GO:0006090 pyruvate metabolic process GO:0019752 carboxylic acid metabolic process GO:0032787 monocarboxylic acid metabolic process GO:0043648 dicarboxylic acid metabolic process GO:0046395 carboxylic acid catabolic process GO:0046394 carboxylic acid biosynthetic process GO:0006520 cellular amino acid metabolic process GO:0006631 fatty acid metabolic process GO:0072329 monocarboxylic acid catabolic process GO:0046487 glyoxylate metabolic process GO:0019318 hexose metabolic process GO:0006139 nucleobase-containing compound metabolic process GO:0006006 glucose metabolic process GO:1901293 nucleoside phosphate biosynthetic process GO:1901659 glycosyl compound biosynthetic process GO:1901566

• rganonitrogen compound

biosynthetic process GO:0090407

• rganophosphate

biosynthetic process GO:1901362

• rganic cyclic compound

biosynthetic process GO:1901137 carbohydrate derivative biosynthetic process GO:0035384 thioester biosynthetic process GO:0006107

• xaloacetate metabolic

process GO:0006536 glutamate metabolic process GO:0006103 2-oxoglutarate metabolic process GO:0016042 lipid catabolic process GO:0051188 cofactor biosynthetic process GO:0018130 heterocycle biosynthetic process GO:0019438 aromatic compound biosynthetic process GO:0044271 cellular nitrogen compound biosynthetic process GO:0044272 sulfur compound biosynthetic process GO:0043094 cellular metabolic compound salvage GO:0030258 lipid modification GO:0044242 cellular lipid catabolic process GO:0009605 response to external stimulus GO:0009991 response to extracellular stimulus GO:0031667 response to nutrient levels GO:0042221 response to chemical GO:0009719 response to endogenous stimulus GO:0007584 response to nutrient GO:0010033 response to organic substance GO:0009725 response to hormone GO:1901700 response to

• xygen-containing

compound GO:0042493 response to drug GO:0010035 response to inorganic substance GO:1990267 response to transition metal nanoparticle GO:0045454 cell redox homeostasis GO:0042592 homeostatic process GO:0050794 regulation of cellular process GO:0048519 negative regulation of biological process GO:0048583 regulation of response to stimulus GO:0051239 regulation of multicellular organismal process GO:1900046 regulation of hemostasis GO:0065008 regulation of biological quality GO:0050878 regulation of body fluid levels GO:0009062 fatty acid catabolic process GO:0019395 fatty acid oxidation GO:0046700 heterocycle catabolic process GO:0006635 fatty acid beta-oxidation GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:1901606 alpha-amino acid catabolic process GO:0034440 lipid oxidation GO:0046113 nucleobase catabolic process GO:0009063 cellular amino acid catabolic process GO:1901565

• rganonitrogen compound

catabolic process GO:1901361

• rganic cyclic compound

catabolic process GO:0006749 glutathione metabolic process GO:0042558 pteridine-containing compound metabolic process GO:0009112 nucleobase metabolic process GO:0072521 purine-containing compound metabolic process GO:0009116 nucleoside metabolic process GO:0072524 pyridine-containing compound metabolic process GO:0006518 peptide metabolic process GO:0006732 coenzyme metabolic process GO:0009108 coenzyme biosynthetic process GO:0006637 acyl-CoA metabolic process GO:0006733

• xidoreduction coenzyme

metabolic process GO:0071616 acyl-CoA biosynthetic process GO:0043603 cellular amide metabolic process GO:1901607 alpha-amino acid biosynthetic process GO:0008652 cellular amino acid biosynthetic process GO:0072522 purine-containing compound biosynthetic process GO:0009163 nucleoside biosynthetic process GO:0009064 glutamine family amino acid metabolic process GO:0006525 arginine metabolic process GO:0009066 aspartate family amino acid metabolic process GO:0009069 serine family amino acid metabolic process GO:0006570 tyrosine metabolic process GO:0009070 serine family amino acid biosynthetic process GO:0006544 glycine metabolic process GO:0006558 L-phenylalanine metabolic process GO:0006545 glycine biosynthetic process GO:0006796 phosphate-containing compound metabolic process GO:0006753 nucleoside phosphate metabolic process GO:0019693 ribose phosphate metabolic process GO:0046390 ribose phosphate biosynthetic process GO:0010038 response to metal ion GO:0010269 response to selenium ion GO:0006084 acetyl-CoA metabolic process GO:0006559 L-phenylalanine catabolic process GO:0009068 aspartate family amino acid catabolic process GO:0006461 protein complex assembly GO:0051259 protein oligomerization GO:0022607 cellular component assembly GO:0043933 macromolecular complex subunit organization GO:0065003 macromolecular complex assembly GO:0071822 protein complex subunit

• rganization

GO:0044085 cellular component biogenesis GO:0070271 protein complex biogenesis GO:0051260 protein homooligomerization GO:0051262 protein tetramerization GO:0051289 protein homotetramerization GO:0034654 nucleobase-containing compound biosynthetic process GO:0006144 purine nucleobase metabolic process GO:0006163 purine nucleotide metabolic process GO:0042278 purine nucleoside metabolic process GO:0009150 purine ribonucleotide metabolic process GO:0006164 purine nucleotide biosynthetic process GO:0009117 nucleotide metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0009141 nucleoside triphosphate metabolic process GO:0009259 ribonucleotide metabolic process GO:0019362 pyridine nucleotide metabolic process GO:0009165 nucleotide biosynthetic process GO:0009119 ribonucleoside metabolic process GO:0046128 purine ribonucleoside metabolic process GO:0042455 ribonucleoside biosynthetic process GO:0009126 purine nucleoside monophosphate metabolic process GO:0009161 ribonucleoside monophosphate metabolic process GO:0009124 nucleoside monophosphate biosynthetic process GO:0009167 purine ribonucleoside monophosphate metabolic process GO:0009127 purine nucleoside monophosphate biosynthetic process GO:0046034 ATP metabolic process GO:0009152 purine ribonucleotide biosynthetic process GO:0046033 AMP metabolic process GO:0009260 ribonucleotide biosynthetic process GO:0009156 ribonucleoside monophosphate biosynthetic process GO:0009168 purine ribonucleoside monophosphate biosynthetic process GO:0046496 nicotinamide nucleotide metabolic process GO:0042451 purine nucleoside biosynthetic process GO:0009144 purine nucleoside triphosphate metabolic process GO:0009199 ribonucleoside triphosphate metabolic process GO:0009205 purine ribonucleoside triphosphate metabolic process GO:0046129 purine ribonucleoside biosynthetic process GO:0045333 cellular respiration GO:0009060 aerobic respiration GO:0001889 liver development GO:0007275 multicellular organism development GO:0048731 system development GO:0048856 anatomical structure development GO:0048732 gland development GO:0048513 animal organ development GO:0061008 hepaticobiliary system development GO:0030193 regulation of blood coagulation GO:0030195 negative regulation of blood coagulation GO:0042730 fibrinolysis GO:0032101 regulation of response to external stimulus GO:0032102 negative regulation of response to external stimulus GO:0061045 negative regulation of wound healing GO:0048585 negative regulation of response to stimulus GO:0051241 negative regulation of multicellular organismal process GO:1900047 negative regulation of hemostasis GO:0080134 regulation of response to stress GO:1903035 negative regulation of response to wounding GO:0050818 regulation of coagulation GO:0050819 negative regulation of coagulation GO:0061041 regulation of wound healing GO:1903034 regulation of response to wounding

GO:0001726 ruffle GO:0005575 cellular_component GO:0005623 cell GO:0044464 cell part GO:0043226

• rganelle

GO:0030054 cell junction GO:0005576 extracellular region GO:0044421 extracellular region part GO:0044422

• rganelle part

GO:0032991 macromolecular complex GO:0044456 synapse part GO:0045202 synapse GO:0099512 supramolecular fiber GO:0031012 extracellular matrix GO:0016020 membrane GO:0044420 extracellular matrix component GO:0031252 cell leading edge GO:0042995 cell projection GO:0043005 neuron projection GO:0044463 cell projection part GO:0098858 actin-based cell projection GO:0005622 intracellular GO:0044424 intracellular part GO:0071944 cell periphery GO:0097458 neuron part GO:0044297 cell body GO:0005886 plasma membrane GO:0043209 myelin sheath GO:0030496 midbody GO:0097708 intracellular vesicle GO:0005856 cytoskeleton GO:0015629 actin cytoskeleton GO:0030863 cortical cytoskeleton GO:0044430 cytoskeletal part GO:0099513 polymeric cytoskeletal fiber GO:0043228 non-membrane-bounded

• rganelle

GO:0043229 intracellular organelle GO:0043227 membrane-bounded

• rganelle

GO:0043230 extracellular organelle GO:0043232 intracellular non-membrane-bounded

• rganelle

GO:0044446 intracellular organelle part GO:0043231 intracellular membrane-bounded

• rganelle

GO:0043292 contractile fiber GO:0005737 cytoplasm GO:0044444 cytoplasmic part GO:0005912 adherens junction GO:0005924 cell-substrate adherens junction GO:0070161 anchoring junction GO:0030055 cell-substrate junction GO:0005911 cell-cell junction GO:0005925 focal adhesion GO:0070062 extracellular exosome GO:1903561 extracellular vesicle GO:0031982 vesicle GO:0031988 membrane-bounded vesicle GO:0016023 cytoplasmic, membrane-bounded vesicle GO:0005578 proteinaceous extracellular matrix GO:0005604 basement membrane GO:0099568 cytoplasmic region GO:0031410 cytoplasmic vesicle GO:0005938 cell cortex GO:0044448 cell cortex part GO:0005829 cytosol GO:0044449 contractile fiber part GO:0005884 actin filament GO:0032432 actin filament bundle GO:0042641 actomyosin GO:0043234 protein complex GO:0030425 dendrite GO:0036477 somatodendritic compartment GO:0030424 axon GO:0048770 pigment granule GO:0098805 whole membrane GO:0042383 sarcolemma GO:0042470 melanosome GO:0030016 myofibril GO:0030017 sarcomere GO:0001725 stress fiber GO:0097517 contractile actin filament bundle GO:0005902 microvillus

GO:0005575 cellular_component GO:0005623 cell GO:0044464 cell part GO:0043226

• rganelle

GO:0031974 membrane-enclosed lumen GO:0044422

• rganelle part

GO:0016020 membrane GO:0005576 extracellular region GO:0044421 extracellular region part GO:0032991 macromolecular complex GO:0044425 membrane part GO:0005622 intracellular GO:0044424 intracellular part GO:1990204

• xidoreductase complex

GO:0031975 envelope GO:0012505 endomembrane system GO:0043209 myelin sheath GO:0005737 cytoplasm GO:0044444 cytoplasmic part GO:0043229 intracellular organelle GO:0044446 intracellular organelle part GO:0019866

• rganelle inner membrane

GO:0005739 mitochondrion GO:0044429 mitochondrial part GO:0098798 mitochondrial protein complex GO:0043227 membrane-bounded

• rganelle

GO:0043230 extracellular organelle GO:0043231 intracellular membrane-bounded

• rganelle

GO:0031967

• rganelle envelope

GO:0031090

• rganelle membrane

GO:0031982 vesicle GO:0005783 endoplasmic reticulum GO:0042579 microbody GO:0044438 microbody part GO:0005829 cytosol GO:0045239 tricarboxylic acid cycle enzyme complex GO:0005759 mitochondrial matrix GO:0043233

• rganelle lumen

GO:0070013 intracellular organelle lumen GO:0005740 mitochondrial envelope GO:0031966 mitochondrial membrane GO:0044455 mitochondrial membrane part GO:0031907 microbody lumen GO:0005743 mitochondrial inner membrane GO:0098800 inner mitochondrial membrane protein complex GO:0098796 membrane protein complex GO:0070062 extracellular exosome GO:1903561 extracellular vesicle GO:0031988 membrane-bounded vesicle GO:0005790 smooth endoplasmic reticulum GO:0005777 peroxisome GO:0044439 peroxisomal part GO:0005782 peroxisomal matrix GO:0043234 protein complex GO:1902494 catalytic complex

GO:0003674 molecular_function GO:0003824 catalytic activity GO:0005488 binding GO:0009055 electron carrier activity GO:0016209 antioxidant activity GO:0016740 transferase activity GO:0016853 isomerase activity GO:0016491

• xidoreductase activity

GO:0016829 lyase activity GO:0016787 hydrolase activity GO:0000166 nucleotide binding GO:0051287 NAD binding GO:0050660 flavin adenine dinucleotide binding GO:0050661 NADP binding GO:0036094 small molecule binding GO:0097159

• rganic cyclic compound

binding GO:1901363 heterocyclic compound binding GO:0043167 ion binding GO:0048037 cofactor binding GO:1901681 sulfur compound binding GO:0005515 protein binding GO:0051540 metal cluster binding GO:0002054 nucleobase binding GO:1901265 nucleoside phosphate binding GO:0031406 carboxylic acid binding GO:0016597 amino acid binding GO:0043168 anion binding GO:0043169 cation binding GO:0030170 pyridoxal phosphate binding GO:0046872 metal ion binding GO:0016746 transferase activity, transferring acyl groups GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups GO:0016769 transferase activity, transferring nitrogenous groups GO:0016747 transferase activity, transferring acyl groups

• ther than amino-acyl

groups GO:0016860 intramolecular

• xidoreductase activity

GO:0016863 intramolecular

• xidoreductase activity,

transposing C=C bonds GO:0016614

• xidoreductase activity,

acting on CH-OH group of donors GO:0016645

• xidoreductase activity,

acting on the CH-NH group

• f donors

GO:0016627

• xidoreductase activity,

acting on the CH-CH group

• f donors

GO:0016903

• xidoreductase activity,

acting on the aldehyde or

• xo group of donors

GO:0000062 fatty-acyl-CoA binding GO:0050662 coenzyme binding GO:0003857 3-hydroxyacyl-CoA dehydrogenase activity GO:0016616

• xidoreductase activity,

acting on the CH-OH group

• f donors, NAD or NADP as

acceptor GO:0004300 enoyl-CoA hydratase activity GO:0016835 carbon-oxygen lyase activity GO:0016830 carbon-carbon lyase activity GO:0016836 hydro-lyase activity GO:0016646

• xidoreductase activity,

acting on the CH-NH group

• f donors, NAD or NADP as

acceptor GO:0042802 identical protein binding GO:0046983 protein dimerization activity GO:0042803 protein homodimerization activity GO:0003995 acyl-CoA dehydrogenase activity GO:0016628

• xidoreductase activity,

acting on the CH-CH group

• f donors, NAD or NADP as

acceptor GO:0051536 iron-sulfur cluster binding GO:0016620

• xidoreductase activity,

acting on the aldehyde or

• xo group of donors, NAD
• r NADP as acceptor

GO:0004165 dodecenoyl-CoA delta-isomerase activity GO:0016831 carboxy-lyase activity GO:0004364 glutathione transferase activity GO:0008483 transaminase activity GO:0036137 kynurenine aminotransferase activity GO:0016212 kynurenine-oxoglutarate transaminase activity GO:0070402 NADPH binding GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds GO:0016812 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides