title: Arsenite-induced changes in hepatic protein abundance in cynomolgus monkeys (Macaca fascicularis).
abstract: Arsenic is an environmental pollutant, and its liver toxicity has long been recognized. The effect of arsenic on liver protein expression was analyzed using a proteomic approach in monkeys. Monkeys were orally administered sodium arsenite (SA) for 28 days. As shown by 2D-PAGE in combination with MS, the expression levels of 16 proteins were quantitatively changed in SA-treated monkey livers compared to control-treated monkey livers. Specifically, the levels of two proteins, mortalin and tubulin beta chain, were increased, and 14 were decreased, including plastin-3, cystathionine-beta-synthase, selenium-binding protein 1, annexin A6, alpha-enolase, phosphoenolpyruvate carboxykinase-M, erlin-2, and arginase-1. In view of their functional roles, differential expression of these proteins may contribute to arsenic-induced liver toxicity, including cell death and carcinogenesis. Among the 16 identified proteins, four were selected for validation by Western blot and immunohistochemistry. Additional Western blot analyses indicated arsenic-induced dysregulation of oxidative stress related, genotoxicity-related, and glucose metabolism related proteins in livers from SA-treated animals. Many changes in the abundance of toxicity-related proteins were also demonstrated in SA-treated human hepatoma cells. These data on the arsenic-induced regulation of proteins with critical roles may help elucidate the specific mechanisms underlying arsenic-induced liver toxicity.
authors.affiliation: BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Soohee
authors.initials: S
authors.lastname: Kim
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seungwoo
authors.initials: S
authors.lastname: Lee
authors.forename: Jung-Duck
authors.initials: JD
authors.lastname: Park
authors.forename: Doug-Young
authors.initials: DY
authors.lastname: Ryu
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D015180:Electrophoresis, Gel, Two-Dimensional; D056945:Hep G2 Cells; D006651:Histocytochemistry; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D011506:Proteins / Q000032:analysis* / Q000378:metabolism; D020543:Proteome / Q000187:drug effects*; D040901:Proteomics; D017670:Sodium Compounds / Q000633:toxicity*
chemical_list: D018053:Arsenites; D011506:Proteins; D020543:Proteome; D017670:Sodium Compounds; C017947:sodium arsenite
keywords: Animal proteomics; Arsenic; Liver; Monkey; Toxicity