Abstract
We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP) to induce a current (mainly Na(+)) increased the formation of nitric oxide (NO), as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF) with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated ove...Continue Reading
References
Oct 21, 1976·Journal of Theoretical Biology·G Burnstock
Oct 19, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·B HuB T Liang
Oct 26, 2005·Journal of Molecular and Cellular Cardiology·Cristina BanfiMaria P Abbracchio
Feb 2, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jian-Bing ShenBruce T Liang
Apr 29, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·John W ElrodDavid J Lefer
Jul 22, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Dmitry SoninBruce T Liang
Feb 10, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Jian-Bing ShenBruce T Liang
Feb 24, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Hanny MusaHalina Dobrzynski
Jun 12, 2009·Molecular Pain·Makoto TsudaKazuhide Inoue
Nov 19, 2009·The Journal of Clinical Investigation·Hiroyuki NakayamaJeffery D Molkentin
Apr 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lindsey E McQuadeStephen J Lippard
Feb 5, 2011·Current Medicinal Chemistry·A J SzentmiklósiP P Nánási
Mar 8, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Yuichiro OhataToshiaki Kawai
Sep 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Juliano L SartorettoThomas Michel
Aug 4, 2012·Circulation Research·Ronghua Yang, Bruce T Liang
Jan 3, 2013·The Journal of Clinical Investigation·Saptarsi M Haldar, Jonathan S Stamler
Oct 3, 2013·PloS One·Mitrajit GhoshMarc A M J van Zandvoort
Mar 14, 2014·Circulation. Heart Failure·Tiehong YangBruce T Liang
Citations
Jun 23, 2019·Cell Biology International·Zilin WangShangdong Liang
Feb 23, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sang Jun HanH Thomas Lee
Aug 15, 2020·Purinergic Signalling·Kenneth A Jacobson
Oct 16, 2019·Frontiers in Pharmacology·Bruno BragançaPaulo Correia-de-Sá
Aug 10, 2019·Frontiers in Cellular Neuroscience·Sheraz KhojaDaryl L Davies
Jun 2, 2020·Frontiers in Pharmacology·Leanne StokesElizabeth Allum
Feb 4, 2021·International Journal of Molecular Sciences·Muhammad AslamRainer Schulz