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Arsenite‐induced changes in hepatic protein abundance in cynomolgus monkeys ( Macaca fascicularis )
Author(s) -
Kim Soohee,
Lee Seung Heon,
Lee Seungwoo,
Park JungDuck,
Ryu DougYoung
Publication year - 2014
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300509
Subject(s) - arsenic toxicity , western blot , toxicity , sodium arsenite , biology , microbiology and biotechnology , arsenic , annexin a2 , arsenic trioxide , heat shock protein , biochemistry , chemistry , annexin , apoptosis , organic chemistry , gene
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.