title: Comparative Proteomics Analysis Reveals L-Arginine Activates Ethanol Degradation Pathways in HepG2 Cells.
abstract: L-Arginine (Arg) is a versatile amino acid that plays crucial roles in a wide range of physiological and pathological processes. In this study, to investigate the alteration induced by Arg supplementation in proteome scale, isobaric tags for relative and absolute quantification (iTRAQ) based proteomic approach was employed to comparatively characterize the differentially expressed proteins between Arg deprivation (Ctrl) and Arg supplementation (+Arg) treated human liver hepatocellular carcinoma (HepG2) cells. A total of 21 proteins were identified as differentially expressed proteins and these 21 proteins were all up-regulated by Arg supplementation. Six amino acid metabolism-related proteins, mostly metabolic enzymes, showed differential expressions. Intriguingly, Ingenuity Pathway Analysis (IPA) based pathway analysis suggested that the three ethanol degradation pathways were significantly altered between Ctrl and +Arg. Western blotting and enzymatic activity assays validated that the key enzymes ADH1C, ALDH1A1, and ALDH2, which are mainly involved in ethanol degradation pathways, were highly differentially expressed, and activated between Ctrl and +Arg in HepG2 cells. Furthermore, 10 mM Arg significantly attenuated the cytotoxicity induced by 100 mM ethanol treatment (P < 0.0001). This study is the first time to reveal that Arg activates ethanol degradation pathways in HepG2 cells.
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Guokai
authors.initials: G
authors.lastname: Yan
authors.affiliation: Faculty of Animal and Agricultural Sciences, Diponegoro University, Tembalang Campus, Semarang 50275, Central Java, Indonesia.
authors.forename: Retno
authors.initials: R
authors.lastname: Lestari
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Baisheng
authors.initials: B
authors.lastname: Long
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Fan
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Zhichang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Xingya
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: Faculty of Animal and Agricultural Sciences, Diponegoro University, Tembalang Campus, Semarang 50275, Central Java, Indonesia.
authors.forename: Agung
authors.initials: A
authors.lastname: Purnomoadi
authors.affiliation: Faculty of Animal and Agricultural Sciences, Diponegoro University, Tembalang Campus, Semarang 50275, Central Java, Indonesia.
authors.forename: Joelal
authors.initials: J
authors.lastname: Achmadi
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yan
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D053858:Metabolic Networks and Pathways; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D050697:Retinal Dehydrogenase; D021241:Spectrometry, Mass, Electrospray Ionization; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D020543:Proteome; D000431:Ethanol; D001120:Arginine; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase