关键词: 
molecular mechanisms /
protein phosphatase /
cell proliferation /
Gene Ontology /
liver cells

摘要: Trichloroethylene (TCE) is a major pollutant that affects both occupational and general environments[1].The liver is an important target organ of TCE[1].Substantial efforts and remarkable progress into understanding TCE cytotoxicity have been made in cultured liver cells.However,the molecular mechanisms by which TCE induces hepatotoxicity are not well understood.SET (also known as protein phosphatase 2A inhibitor,I2PP2A,or template-activating factor-Ⅰ,TAF-Ⅰ) is a nuclear protein that regulates histone modification,gene transcription,DNA replication,nucleosome assembly,phosphatase activity and kinase activity[2].Previously,we observed a significant TCE-induced up-regulation of SET in human hepatic L-02 cells[3].We further reported that the knockdown of SET significantly attenuated TCE-induced cytotoxicity,rescued the inhibition of PP2A activity,and suppressed the activation of caspase-3 mediated by TCE treatment in L-02 cells.Recently,we identified 42 novel Gene Ontology (GO) co-annotated SET-binding proteins and revealed the effects of TCE on the distribution and interactions of SET and its binding partners,eEF1A1 and eEF1A2,in L-02 cells[4].Herein,we describe a biphasic concentration-response in both cell proliferation and the expression of SET-associated proteins to TCE treatment of L-02 cells.Our results suggest that the TCE-induced alterations in the expression of SET and its binding partners may be involved in the biphasic effect induced by TCE and partially constitute the mechanisms leading to TCE hepatotoxicity.