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NOX3‐derived reactive oxygen species promote TNF‐α‐induced reductions in hepatocyte glycogen levels via a JNK pathway
Author(s) -
Li Lanfang,
He Qinghua,
Huang Xiuqing,
Man Yong,
Zhou Yingsheng,
Wang Shu,
Wang Jianye,
Li Jian
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.01.044
Subject(s) - nadph oxidase , reactive oxygen species , insulin resistance , hepatocyte , endocrinology , medicine , protein kinase b , phosphorylation , glycogen synthase , biology , glycogen , chemistry , microbiology and biotechnology , biochemistry , insulin , in vitro
TNF‐α‐induced insulin resistance is associated with generation of reactive oxygen species (ROS). This study aims at defining the link between ROS production and hepatic insulin resistance. Treatment with TNF‐α increased ROS generation through activating NADPH oxidase 3 (NOX3) in HepG2 hepatocytes. Down‐regulation of NOX3 using siRNA prevented TNF‐α‐induced decrease of cellular glycogen. In the cells treated with TNF‐α, there were NOX3‐dependent activation of JNK, inhibition of IRS1 and phosphorylation of AKT/PKB and GSK. In conclusion, the effects of TNF‐α on hepatic insulin resistance appear to be, at least in part, mediated by NOX3‐derived ROS through a JNK pathway.