The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Gemfibrozil, a lipid-lowering drug, inhibits the induction of nitric-oxide synthase in human astrocytes.

Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astrocytes. Similar to gemfibrozil, clofibrate, another fibrate drug, also inhibited the expression of iNOS. Inhibition of human iNOS promoter-driven luciferase activity by gemfibrozil in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of iNOS. Since gemfibrozil is known to activate peroxisome proliferator-activated receptor-alpha (PPAR-alpha), we investigated the role of PPAR-alpha in gemfibrozil- mediated inhibition of iNOS. Gemfibrozil induced peroxisome proliferator-responsive element (PPRE)-dependent luciferase activity, which was inhibited by the expression of DeltahPPAR-alpha, the dominant-negative mutant of human PPAR-alpha. However, DeltahPPAR-alpha was unable to abrogate gemfibrozil-mediated inhibition of iNOS suggesting that gemfibrozil inhibits iNOS independent of PPAR-alpha. The human iNOS promoter contains consensus sequences for the binding of transcription factors, including interferon-gamma (IFN-gamma) regulatory factor-1 (IRF-1) binding to interferon-stimulated responsive element (ISRE), signal transducer and activator of transcription (STAT) binding to gamma-activation site (GAS), nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and CCAAT/enhancer-binding protein beta (C/EBPbeta); therefore, we investigated the effect of gemfibrozil on the activation of these transcription factors. The combination of interleukin (IL)-1beta and IFN-gamma induced the activation of NF-kappaB, AP-1, C/EBPbeta, and GAS but not that of ISRE, suggesting that IRF-1 may not be involved in cytokine- induced expression of iNOS in human astrocytes. Interestingly, gemfibrozil strongly inhibited the activation of NF-kappaB, AP-1, and C/EBPbeta but not that of GAS in cytokine-stimulated astroglial cells. These results suggest that gemfibrozil inhibits the induction of iNOS probably by inhibiting the activation of NF-kappaB, AP-1, and C/EBPbeta and that gemfibrozil, a prescribed drug for humans, may further find its therapeutic use in neuroinflammatory diseases.[1]


  1. Gemfibrozil, a lipid-lowering drug, inhibits the induction of nitric-oxide synthase in human astrocytes. Pahan, K., Jana, M., Liu, X., Taylor, B.S., Wood, C., Fischer, S.M. J. Biol. Chem. (2002) [Pubmed]
WikiGenes - Universities