Studies from Washington University Provide New Data on Nitric Oxide (Fumagillin Prodrug Nanotherapy Suppresses Macrophage Inflammatory Response via Endothelial Nitric Oxide)
By a News Reporter-Staff News Editor at Health & Medicine Week -- Investigators publish new report on Nitric Oxide. According to news reporting from St. Louis, Missouri, by NewsRx journalists, research stated, "Antiangiogenesis has been extensively explored for the treatment of a variety of cancers and certain inflammatory processes. Fumagillin, a mycotoxin produced by Aspergillus fumigatus that binds methionine aminopeptidase 2 (MetAP-2), is a potent antiangiogenic agent."
The news correspondents obtained a quote from the research from Washington University, "Native fumagillin, however, is poorly soluble and extremely unstable. We have developed a lipase-labile fumagillin prodrug (Fum-PD) that eliminated the photoinstability of the compound. Using alpha(v)beta(3)-integrin-targeted perfluorocarbon nanocarriers to deliver Fum-PD specifically to angiogenic vessels, we effectively suppressed clinical disease in an experimental model of rheumatoid arthritis (RA). The exact mechanism by which Fum-PD-loaded targeted nanoparticles suppressed inflammation in experimental RA, however, remained unexplained. We herein present evidence that Fum-PD nanotherapy indirectly suppresses inflammation in experimental RA through the local production of endothelial nitric oxide (NO). Fum-PD-induced NO activates AMP-activated protein kinase (AMPK), which subsequently modulates macrophage inflammatory response. In vivo, NO-induced AMPK activation inhibits mammalian target of rapamycin (mTOR) activity and enhances autophagic flux, as evidenced by p62 depletion and increased autolysosome formation. Autophagy in turn mediates the degradation of IkappaB kinase (IKK), suppressing the NF-kappa B p65 signaling pathway and inflammatory cytokine release. Inhibition of NO production by N-G-nitro-L-arginine methyl ester (L-NAME), a NUR oxide synthase inhibitor, reverses the suppression of NF-kappa B-mediated inflammatory response Induced by Fum-PD nanotherapy."
According to the news reporters, the research concluded: "These unexpected results uncover an activity of Fum-PD nanotherapy that may be further explored in the treatment of angiogenesis-dependent diseases."
For more information on this research see: Fumagillin Prodrug Nanotherapy Suppresses Macrophage Inflammatory Response via Endothelial Nitric Oxide. ACS Nano, 2014;8(7):7305-7317. ACS Nano can be contacted at: Amer Chemical Soc, 1155 16TH St, NW, Washington, DC 20036, USA. (American Chemical Society - www.acs.org; ACS Nano - www.pubs.acs.org/journal/ancac3)
Our news journalists report that additional information may be obtained by contacting H.F. Zhou, Washington University, Sch Med, Dept. of Med, Div Cardiol, St Louis, MO 63110, United States. Additional authors for this research include H.M. Yan, Y. Hu, L.E. Springer, X.X. Yang, S.A. Wickline, D.P.J. Pan, G.M. Lanza and C.T.N. Pham (see also Nitric Oxide).
Keywords for this news article include: Kinase, Missouri, St. Louis, Chemicals, Chemistry, Immunology, Macrophages, Inflammation, Nitric Oxide, United States, Nitrogen Oxides, Enzymes and Coenzymes, North and Central America, Reactive Nitrogen Species, Mononuclear Phagocyte System
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