HAN Fei 1 SUN Jin 2 ZHOU Meng-liang 3 YU Ting-ting 1

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1 13 6 Vol13 No Life Science Research Dec 200 1, 2, 3 1, :,, C E 3, highwire, DAVID GO pathway express GO, 3 14, GO, 3, 3, : ; ; ; GO ; : Q343 : A : (200) Genes and Common Pathways Related to Three Food Antioxidant Revealed by Combining and Analyzing Candidate Gene Lists from Multiple Technology Platforms HAN Fei 1 SUN Jin 2 ZHOU Meng-liang 3 YU Ting-ting 1 1 Academy of State Administration of Grain Beijing China 2 School of Food Science and Technology Jiangnan University Wuxi Jiangsu China 3 College of Bioscience and Biotechnology Yangzhou University Yangzhou : : Jiangsu China Abstract Antioxidants modulate body gene expression and regulate wide biological process Antioxidants related genes are studied using different technology storing in peer reviewed articles Exploring the relationship between these genes is helpful for finding their function mechanism and for development of novel biomarker for new antioxidant screening The gene related to three typical antioxidants retinoic acid vit C and vit E were dig out from articles searching from highwire database The significantly related GO biological terms and gene pathway were analyzed using DAVID tools and pathway express respectively The results showed that 14 genes were commonly related to three antioxidants Similar GO biological and gene pathway were involved in three antioxidants including cell communication immune response apoptosis cell cycle and several typical signaling pathways was the common pathways related three antioxidants implying they modulated cell cycle regulation cytoskeleton assembly adhesion migration motion growth regulation survival and angiogenesis etc They might inhibit tumorigenesis development and invasion targeting to focal adhesion Key words antioxidants gene expression gene pathway GO term focal adhesion Life Science Research ~41 : 73- Tel hf@chinagrainorg

2 [1] highwire http //wwwhighwireorg vitc vite 1 retinoic acid AND review 2 retinoic acid AND gene OR microarray OR proteomics 3 vitc AND review ROS reactive oxygen species 4 vitc AND gene OR microarray OR proteomics 5 ascorbic acid AND review [2,3] 6 ascorbic acid AND gene OR microarray OR proteomics 7 vite AND review 8 vite AND gene OR microarray OR proteomics 80 - [1,4] PCR [4] GO DAVID http //davidabccncifcrfgov/ [5~] GO P 122 pathway express http //vortexcswayne [10] edu/ontoexpress / vitc vite [ 11,12] vitc vite IF P 2 21 vitc vite E vite 2 05 C vitc Retinoic acid vitc vite vitc vite 14

3 6 : 48 SOD1 SOD2 GPX4 Fos GAS6 TOP2A CDKN1A timp1 clu Table 1 1 vitc vite The common related gene pathway of vitc, vite and retinoic acid Gene symbol Gene name Gene function SOD1 SOD2 Gpx4 CDKN1A Anxa5 Timp1 Clu Fos COL1A1 Pecam1 Mgp Cd44 GAS6 TOP2A Superoxide dismutase 1 Superoxide dismutase 2 Glutathione peroxidase 4 Cyclin-dependent kinase inhibitor 1A Annexin A5 TIMP metallopeptidase inhibitor 1 Clusterin FBJ osteosarcoma oncogene Collagen type I alpha 1 Platelet/ endothelial cell adhesion molecule 1 Matrix Gla protein Cd44 molecule Growth arrest specific 6 Topoisomerase DNA II alpha 170 kda Inhibition of the reactions brought about by dioxygen O 2 or peroxides Catalysis of an oxidation redox reaction Catalysis of an oxidation redox reaction, DNA repair cell apoptosis Negative regulation of coagulation Negative regulation of membrance protein ectodomain proteolysis, response to organic substance, response to peptide hormone stimulus Anti-apoptosis Oxidative stress reaction Leukocyte migration Construction of extracellular matrix Cell metabolism regulation DNA copy 22 vitc vite GO Pathway express GO Gene Ontology Consortium 1 3 GF RTK C PKC Ha- [13] Ras Filamin RhoA vitc vite Actin Rac c-jun JNK UNIGEN id DAVID GO ERK1/2 Elk1 2 Bcl-2 GO 3 vite GO 10 vitc GO S- 4 cell cycle [14] focal adhesion 3 GO ROS 23 vite 3 vitc vite Nrf2 PPAR signaling pathway TGF-beta signaling pathway Pathway express NAD P H NQO1 ARE VE ARE vitc [15] KEAP1 24 vitc vite 14 vitc vite vitc vite SOD1 SOD2

4 Gpx4 3 [16] VitC 3 GO Cip1 / p21 [17] cell cycle IF 2 3 GO Table 2 The significantly related GO biological terms of three antioxidants Gene ontology Gene number Ratio/ % P-value Retinoic acid Cell communication Adipocyte signaling pathway Regulation of action cytoskeleton B cell receptor signaling pathway Hematopoietic cell lineage Complement and coagulation cascade Adherens junction Cell adhesion molecule TGF-β signaling pathway Dorso-ventral axis formation WNT signaling pathway Apoptosis Cytokine-cytokine receptor interaction MAPK signaling pathway vitc Cell communication vite Toll-like receptor signaling pathway MAPK signaling pathway Glutathione metabolism TGF-β signaling pathway Fc epsilon ri signaling pathway T cell receptor signaling pathway Hematopoietic cell lineage Table 3 The significantly related gene pathway of three antioxidants Pathway name Impact factor P-value Corrected gamma P-value Retinoic acid PPAR signaling pathway ErbB signaling pathway TGF-beta signaling pathway B cell receptor signaling pathway VitE PPAR signaling pathway TGF-beta signaling pathway E E E

5 6 : 41 RhoGAP mdia1 ECM ECM-receptor interaction ITGA ITGB PKC Src RhoGEF Calpain Actinin Filamin Talin Paxillin PTEN Zyxin VASP Vinculin Parvin ILK RhoA ROCK PIPSK MLCP PIP2 PDK1 Akt/PKB Cdc42 MLCK MLC Actin Regulation of actin cytoskeleton Actin polymerization GSK-3β β-catenin wnt signaling pathway Cell motility Stress fiber /FA formation Filopodia Lamellipodia formation FA turnover Cytokinecytokine receptor interaction Caveolin Fyn FAK GF RTK Shc Grb2 Sos Ha-Ras Raf-1 PI3K p130cas Phosphatidyl inositol signaling system Crk PIP3 GRF2 C3G Vav Rac PAK DOCK1 Rap1 B-Raf MEK1 Apoptosis JNK c-jun ERK1/2 Bad MAPK signaling pathway Bcl-2 E1K1 Cell proliferation CycD DNA Cell survival ciaps DNA Fig1 The common responsive gene pathway of vitc, vite and retinoic acid- focal adhesion [8] BLOCK G PATTERSON B SUBAR A Fruit vegetables and cancer prevention a review of the epidemiological evidence[j] Nutr Cancer [] LIU R H Health benefits of fruits and vegetables are from additive and synergistic combinayion of phytochemicals[j] 3 GO Am J Clin Nutr S-520S [10] BLUMBERG J Use of biomarkers of oxidative stress in research studies[j] J Nutr [11] STOREY J D TIBSHIRANI R Statistical significance for genomewide studies[j] Proc Natl Acad Sci USA [18] [12] DRAGHICI S KHATRI P TARCA A L et al A systems biology approach for pathway level analysis[j] Genome Res [13] ASHBURNER M BALL C A BLAKE J A et al Gene ontology tool for the unification of biology[j] Nat Genet (References): [14] TANAKA H MAKINO Y OKAMOTO K et al Redox [1] VALKO M LEIBFRITZ D MONCOL J et al Free radicals regulation of the nuclear receptor[j] Oncology and antioxidants in normal physiological functions and human Suppl disease[j] The International Journal of Biochemistry & Cell [15] CHEN X L DODD G THOMAS S et al Activation of Biology Nrf2/ARE pathway protects endothelial cells from oxidant [2] AMES B N GOLD L S Endogenous mutagens and the injury and inhibits inflammatory gene expression[j] Am J causes of aging and cancer[j] Mutat Res Physiol Heart Circ Physiol [16] NAHUM A HIRSH K DANILENKO M et al Lycopene [3] HALLIWELL B GUTTERIDGE J M C Free Radicals in inhibition of cell cycle progression in breast and endometrial Biology and Medicine[M] New York Oxford University Press cancer cells is associated with reduction in cyclin D levels and retention of p27 Kip1 in the cyclin E-cdk2 complexes [4] MAYNE S T Antioxidant nutrients and chronic disease use [J] Oncogene of biomarkers of exposure and oxidative stress status in [17] THOMAS C G VEZYRAKI P E KALFAKAKOU V P et al epidemiologic research [J] J Nutr Suppl 3 Vitamin C transiently arrests cancer cell cycle progression in S phase and G2/M boundary by modulating the kinetics of [5] TEMPLE N J Antioxidants and disease More questions than activation and the subcellular localization of Cdc25C answers[j] Nutr Res phosphatase[j] J Cell Physiol [6] WILLETT W C Diet and health what should we eat [J] [18] ROMER L H BIRUKOV K G GARCIA J G Focal Science adhesions paradigm for a signaling nexus [J] Circ Res [7] WILLETT W C Balancing life-style and genomics research for disease prevention[j] Science