Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase

The European Respiratory Journal
Y YangStefan Uhlig

Abstract

Platelet-activating factor (PAF) is a mediator of pulmonary oedema in acute lung injury that increases vascular permeability within minutes, partly through activation of acid sphingomyelinase (ASM). Since caveolae are rich in sphingomyelin and caveolin-1, which block endothelial nitric oxide (NO) synthase (eNOS) by direct binding, we examined the relationship between ASM, caveolin-1 and eNOS activity in the regulation of vascular permeability by PAF. In caveolar fractions from pulmonary vascular endothelial cells (isolated from perfused rat lungs) the abundance of caveolin-1 and eNOS increased rapidly after PAF perfusion. PAF treatment decreased endothelial NO (eNO) formation as assessed by in situ fluorescence microscopy. Restoration of eNO levels with PAPA-NONOate ((Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate) mitigated the PAF-induced oedema. PAF treatment increased the ASM activity in caveolar fractions and perfusion with ASM decreased eNO production. Pharmacological inhibition of the ASM pathway with imipramine, D609 or dexamethasone blocked the PAF-induced increase of caveolin-1 and eNOS in caveolae, and the decrease in eNO production and oedema formation. We conclude that PAF causes ASM-dependent...Continue Reading

Citations

Mar 16, 2011·Clinical and Experimental Pharmacology & Physiology·Jin-Fu XuHui-Ping Li
May 13, 2011·American Journal of Respiratory Cell and Molecular Biology·Steffen KunzmannBoris W Kramer
Dec 14, 2011·Free Radical Biology & Medicine·Peter R Kvietys, D Neil Granger
Apr 21, 2010·Translational Research : the Journal of Laboratory and Clinical Medicine·Wolfgang M Kuebler
Oct 30, 2016·Cardiovascular Therapeutics·Anand Vijaya Kumar Palur RamakrishnanMenge Denis Mingate
Sep 9, 2011·Therapeutic Advances in Respiratory Disease·Yang Yang, Stefan Uhlig
Mar 12, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mark J McVeyWolfgang M Kuebler
Jul 18, 2018·The Journal of Physiology·Szandor SimmonsWolfgang M Kuebler
Mar 1, 2012·American Journal of Respiratory Cell and Molecular Biology·Fatima AnjumRaj Wadgaonkar
Nov 24, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Fabian P S YuJeffrey A Medin
Jul 4, 2017·Frontiers in Immunology·Monika MalczykAkylbek Sydykov
Jun 26, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mark McVeyWolfgang M Kuebler
Oct 19, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Feng WuBryan J McVerry
Apr 14, 2015·Biological Chemistry·Peter L JerniganTimothy A Pritts
Jan 24, 2019·International Journal of Molecular Sciences·Angel CogolludoLaura Moreno
May 16, 2020·Mediators of Inflammation·Lucy K ReissDieter Adam
Feb 6, 2020·American Journal of Respiratory Cell and Molecular Biology·Benjamin Grimmer, Wolfgang M Kuebler
Feb 7, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Wolfgang M KueblerStefan Uhlig

❮ Previous
Next ❯

Related Concepts

Related Feeds

Caveolins & Signal Transduction

Caveolins are small proteins with a hairpin loop conformation that are located in the plasma membrane of various cell types where they bind cholesterol and interact with receptors essential for several signal transduction pathways. Here is the latest research.

Related Papers

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Wolfgang M KueblerStefan Uhlig
Seminars in Cell & Developmental Biology
Zheng CaiMark I Greene
© 2022 Meta ULC. All rights reserved