Involvement of iNOS and NO in TNF-alpha-downregulated resistin gene expression in 3T3-L1 adipocytes.
OBJECTIVE: In order to characterize the regulation of resistin gene expression, we explore the effect of tumornecrosis factor-alpha (TNF-alpha) on resistin mRNA expression and its underlying mechanism in 3T3-L1 adipocytes. METHODS AND PROCEDURES: Differentiated 3T3-L1 adipocytes were treated for 24 h with 0-10 ng/ml of TNF-alpha or with 2.5 ng/ml of TNF-alpha for 0-24 h, and then resistin mRNA levels were measured by northern blotting. To further explore the involvement of nitric oxide (NO) in TNF-alpha-regulated resistin expression, the effect of the NO donor, sodium nitroprusside (SNP), on resistin mRNA levels in adipocytes and the effect of the nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME), and S,S'-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea.2HBr (PBITU), on the TNF-alpha effect in adipocytes were examined. The effects of TNF-alpha on inducible NOS (iNOS) protein expression in adipocytes were also measured by western blotting. RESULTS: Our results showed that TNF-alpha caused a dose-dependent reduction in resistin mRNA levels. This effect seemed to be associated with the TNF-alpha-induced expression of iNOS. The results showed that TNF-alpha induced iNOS expression and release of NO after 24-h treatment of differentiated 3T3-L1 adipocytes. Pretreatment with L-NAME and PBITU significantly reversed the TNF-alpha-induced downregulation of resistin expression, while treatment with SNP mimicked the inhibitory effect of TNF-alpha on resistin expression. In addition, pretreatment with protein tyrosine kinase (PTK) inhibitors, genistein and AG-1288, prevented TNF-alpha-induced iNOS expression and subsequent resistin downregulation. DISCUSSION: Our data suggest that TNF-alpha suppresses resistin expression by inducing iNOS expression, thus causing overproduction of NO, which downregulates resistin gene expression.[1]References
- Involvement of iNOS and NO in TNF-alpha-downregulated resistin gene expression in 3T3-L1 adipocytes. Juan, C.C., Lien, C.C., Chang, C.L., Huang, Y.H., Ho, L.T. Obesity. (Silver. Spring) (2008) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
