title: Rosiglitazone attenuates tumor necrosis factor-α-induced protein-tyrosine phosphatase-1B production in HepG2 cells.
abstract: Tumor necrosis factor (TNF)-α impairs insulin signaling and plays an important role in the development of insulin resistance. The underlying molecular mechanism by which TNF-α regulates hepatic protein-tyrosine phosphatase (PTP)-1B expression is not well understood. Rosiglitazone is used as a drug to improve insulin sensitivity in vivo. However, its effect on TNF-α-induced PTP-1B expression remains to be explored. In the present study, we sought to identify the mechanism of TNF-α-regulated hepatic PTP-1B expression and evaluate the effect of rosiglitazone on TNF-α-induced hepatic PTP-1B upregulation. TNF-α up-regulates PTP- 1B expression in a dose-dependent manner and decreases insulin-stimulated phosphorylation of IR and insulin receptor substrate-1 in HepG2 cells. TNF-α increases p65 protein level and nuclear factor κB (NF-κB) activity. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate impairs TNF-α-induced PTP-1B upregulation. Rosiglitazone significantly blocks TNF-α-induced PTP-1B upregulation and NF-κB activation. Our data strongly suggest that TNF-α-induced PTP-1B overexpression may contribute to hepatic IR in obesity and diabetes, and NF-κB is involved in rosiglitazone attenuated PTP- 1B upregulation by TNF-α.
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: L-J
authors.initials: LJ
authors.lastname: Yang
authors.forename: D-J
authors.initials: DJ
authors.lastname: Zou
mesh_terms: D015153:Blotting, Western; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D055504:Insulin Receptor Substrate Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D008156:Luciferases; D011972:Receptor, Insulin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1