NOX3-derived reactive oxygen species promote TNF-alpha-induced reductions in hepatocyte glycogen levels via a JNK pathway.
TNF-alpha-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-alpha increased ROS generation through activating NADPH oxidase 3 (NOX3) in HepG2 hepatocytes. Down-regulation of NOX3 using siRNA prevented TNF-alpha-induced decrease of cellular glycogen. In the cells treated with TNF-alpha, there were NOX3-dependent activation of JNK, inhibition of IRS1 and phosphorylation of AKT/PKB and GSK. In conclusion, the effects of TNF-alpha on hepatic insulin resistance appear to be, at least in part, mediated by NOX3-derived ROS through a JNK pathway.
Li
Lanfang
L
Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
He
Qinghua
Q
Huang
Xiuqing
X
Man
Yong
Y
Zhou
Yingsheng
Y
Wang
Shu
S
Wang
Jianye
J
Li
Jian
J
D015153:Blotting, Western; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006003:Glycogen / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008565:Membrane Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen; D019255:NADPH Oxidases; C431570:Nox3 protein, human; D048031:JNK Mitogen-Activated Protein Kinases