title: Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO production.
abstract: At low energy density (0.03 mJ/mm2), extracorporeal shock waves (ESW), originally developed for clinical lithotripsy, have successfully been used for anti-inflammatory treatment of soft tissues. Since nitric oxide plays a critical role in inflammation, we hypothesized for ESW to increase NO production in cells. Using human umbilical vein endothelial cells as a model system, we observed that ESW, at low energy density, rapidly induced an enhancement of eNOS activity. In these cells, eNOS activity is modulated by tyrosine- and serine-phosphorylation. ESW shifted eNOS to a less-tyrosine-phosphorylated form, without affecting its serine-phosphorylation, thus accounting for its rapid enzyme activation. LPS/IFN-gamma treatment of human umbilical vein endothelial cells induced a rapid inhibition of eNOS activity and concomitant NF-kappaB activation which were efficiently counteracted by ESW treatment. Therefore, the present results indicate that the molecular mechanism of clinically observed anti-inflammatory action of ESW should include tyrosine-dephosphorylation of eNOS, a successive increase in NO production and suppression of NF-kappaB activation.
authors.affiliation: Department of Neuroscience and Vision, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mariotto
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cavalieri
authors.forename: Ernesto
authors.initials: E
authors.lastname: Amelio
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Ciampa
authors.forename: Alessandra Carcereri
authors.initials: AC
authors.lastname: de Prati
authors.forename: Ernst
authors.initials: E
authors.lastname: Marlinghaus
authors.forename: Sergio
authors.initials: S
authors.lastname: Russo
authors.forename: Hisanori
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008096:Lithotripsy; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D012694:Serine / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D014443:Tyrosine; D012694:Serine; D007371:Interferon-gamma; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III