Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways.
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.
Lee
Meng-Jung
MJ
Department of Life Science, National Central University, Chung-Li City, Taoyuan, Taiwan.
Lin
Heng
H
Liu
Chi-Wei
CW
Wu
Min-Hua
MH
Liao
Wei-Ju
WJ
Chang
Hsin-Huei
HH
Ku
Hui-Chen
HC
Chien
Yeh-Sheng
YS
Ding
Wang-Hsien
WH
Kao
Yung-Hsi
YH
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
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