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PMID:9305915
| Citation |
Hadri, KE, Courtalon, A, Gauthereau, X, Chambaut-Guérin, AM, Pairault, J and Fève, B (1997) Differential regulation by tumor necrosis factor-alpha of beta1-, beta2-, and beta3-adrenoreceptor gene expression in 3T3-F442A adipocytes. J. Biol. Chem. 272:24514-21 |
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| Abstract |
Modulation of beta-adrenoreceptor expression by tumor necrosis factor-alpha (TNF-alpha) was investigated in murine 3T3-F442A adipocytes. TNF-alpha treatment of mature adipocytes decreased beta3-adrenoreceptor mRNA content in a time- and concentration-dependent manner, with a 8.5-fold decrease observed after a 6-h exposure to 300 pM TNF-alpha. beta1-Adrenoreceptor mRNA abundance was slightly decreased by TNF-alpha treatment, while beta2-adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (-)-[125I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-alpha induced a 2-fold decrease in beta3-adrenoreceptor number, a nonsignificant reduction in beta1-subtype population, and a approximately 4.5-fold increase in beta2-adrenoreceptor density. This correlated with a lower EC50 value measured for epinephrine in stimulating adenylyl cyclase, whereas the EC50 value for norepinephrine increased. Nuclear run-on assays on isolated nuclei and mRNA stability measurements showed that TNF-alpha increased both beta2-adrenoreceptor gene transcription and beta2-adrenoreceptor mRNA half-life, while beta1- and beta3-adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-alpha of the three beta-adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte. |
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| Keywords |
3T3 Cells; Adipocytes/drug effects; Adipocytes/metabolism; Animals; Gene Expression Regulation/drug effects; Mice; RNA, Messenger/genetics; RNA, Messenger/metabolism; Radioligand Assay; Receptors, Adrenergic, beta/classification; Receptors, Adrenergic, beta/genetics; Receptors, Adrenergic, beta/metabolism; Transcription, Genetic; Tumor Necrosis Factor-alpha/pharmacology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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