title: Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways.
abstract: Resistin is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation. It can be regulated by sexual hormones. Whether environmental estrogens regulate the production of resistin is still not clear. Using 3T3-L1 adipocytes, we found that octylphenol upregulated resistin mRNA expression in dose- and time-dependent manners. The concentration of octylphenol that increased resistin mRNA levels by 50% was approximately 100 nM within 6 h of treatment. The basal half-life of resistin mRNA induced by actinomycin D was lengthened by octylphenol treatment, suggesting that octylphenol decreases the rate of resistin mRNA degradation. In addition, octylphenol stimulated resistin protein expression and release. The basal half-life of resistin protein induced by cycloheximide was lengthened by octylphenol treatment, suggesting that octylphenol decreases the rate of resistin protein degradation. While octylphenol was shown to increase activities of the estrogen receptor (ER) and MEK1, signaling was demonstrated to be blocked by pretreatment with either ICI-182780 (an ERalpha antagonist) or U-0126 (a MEK1 inhibitor), in which both inhibitors prevented octylphenol-stimulated phosphorylation of ERK. These results imply that ERalpha and ERK are necessary for the octylphenol stimulation of resistin mRNA expression. Moreover, U-0126 antagonized the octylphenol-increased resistin protein expression and release. These data suggest that the way octylphenol signaling increases resistin protein levels is similar to that by which it increases resistin mRNA levels; it is likely mediated through an ERK-dependent pathway. In vivo, octylphenol increased adipose resistin mRNA expression and serum resistin and glucose levels, supporting its in vitro effect.
authors.affiliation: Department of Life Science, National Central University, Chung-Li City, Taoyuan, Taiwan.
authors.forename: Meng-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Heng
authors.initials: H
authors.lastname: Lin
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Wu
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Liao
authors.forename: Hsin-Huei
authors.initials: HH
authors.lastname: Chang
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Ku
authors.forename: Yeh-Sheng
authors.initials: YS
authors.lastname: Chien
authors.forename: Wang-Hsien
authors.initials: WH
authors.lastname: Ding
authors.forename: Yung-Hsi
authors.initials: YH
authors.lastname: Kao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D000077267:Fulvestrant; D006207:Half-Life; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D052243:Resistin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D015854:Up-Regulation; D000098826:Bisphenol A Compounds
chemical_list: D052242:Adiponectin; D001559:Benzhydryl Compounds; D001786:Blood Glucose; D002070:Butadienes; D003513:Cycloheximide; D003609:Dactinomycin; D052244:Endocrine Disruptors; D004958:Estradiol; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D000077267:Fulvestrant; D020738:Leptin; D048369:MAP Kinase Kinase 1; D009570:Nitriles; D019384:Nucleic Acid Synthesis Inhibitors; D010636:Phenols; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D052243:Resistin; C499919:Adipoq protein, mouse; C499623:Retn protein, mouse; C113580:U 0126; C474055:octylphenol; C025256:nonylphenol; C482127:Map2k1 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds