Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice.

Nature Communications
Norbert WeissmannAlexander Dietrich

Abstract

Lung ischaemia-reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2(y/-)) or the classical transient receptor potential channel 6 (TRPC6(-/-)) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca(2+) influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2(y/-) cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE.

References

Jan 1, 1990·Journal of Applied Physiology·G M DeebM L Morganroth
Aug 1, 1990·The Annals of Thoracic Surgery·R PillaiW A Baumgartner
Sep 21, 1995·Nature·D JolyD Lachaise
Jun 1, 1995·The Journal of Surgical Research·M J EppingerP A Ward
Feb 1, 1996·American Journal of Respiratory and Critical Care Medicine·M E ErasmusJ Prop
Jun 1, 1997·The Journal of Thoracic and Cardiovascular Surgery·B HausenH G Borst
Jan 3, 2001·The Journal of Cell Biology·R J BotelhoS Grinstein
Apr 3, 2001·The Journal of Biological Chemistry·K Hirota, G L Semenza
Apr 21, 2001·Cardiovascular Drug Reviews·L C AddingL E Gustafsson
Jun 1, 2001·The Journal of Thoracic and Cardiovascular Surgery·S M FiserI L Kron
Apr 17, 2002·Circulation·Claude Lenfant
Feb 18, 2003·American Journal of Respiratory and Critical Care Medicine·Marc de PerrotShaf Keshavjee
Jun 18, 2003·The Journal of Biological Chemistry·Tomohiro MurakamiHideo Kanoh
Jul 25, 2003·The Journal of Thoracic and Cardiovascular Surgery·Babu V NaiduMichael S Mulligan
Aug 28, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Ikuo MatsuzakiAron B Fisher
Jan 18, 2005·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Takayuki NakamuraHans-Joachim Schäfers
Apr 26, 2005·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Niels P van der KaaijAd J J C Bogers
Jun 23, 2005·Pflügers Archiv : European journal of physiology·Alexander DietrichThomas Gudermann
Aug 2, 2005·Respiratory Research·Norbert WeissmannFriedrich Grimminger
Aug 2, 2005·Molecular and Cellular Biology·Alexander DietrichLutz Birnbaumer
Dec 24, 2005·Physiological Reviews·Dolly Mehta, Asrar B Malik
Jan 3, 2006·FEBS Letters·Gaetan GavazziKarl-Heinz Krause
Mar 24, 2006·Nature Methods·Vsevolod V BelousovSergey Lukyanov
Jul 25, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Minqing ZhaoVictor E Laubach
Nov 7, 2006·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Chinnaswamy TiruppathiAsrar B Malik
Dec 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Norbert WeissmannThomas Gudermann
Apr 17, 2007·Cell Calcium·Alexander DietrichThomas Gudermann
Apr 21, 2007·Journal of Applied Physiology·Amy ForbesRuud Veldhuizen
Jun 21, 2007·Annual Review of Biochemistry·Kartik Venkatachalam, Craig Montell
Jul 25, 2007·Pflügers Archiv : European journal of physiology·Alexander DietrichThomas Gudermann
Jul 31, 2007·Cell·Manuel ColladoManuel Serrano
Nov 16, 2007·Kidney & Blood Pressure Research·Zhangping Peng, William J Arendshorst
Dec 8, 2007·The Biochemical Journal·Isabel MéridaErnesto Merino
May 30, 2008·Pharmacology & Therapeutics·Hiroyuki WatanabeHiroshi Ito
Sep 13, 2008·American Journal of Respiratory Cell and Molecular Biology·Zequan YangVictor E Laubach
Jan 28, 2009·The Journal of Experimental Medicine·Hanna KorhonenStefan Offermanns
Mar 31, 2009·The Journal of Thoracic and Cardiovascular Surgery·Bart P van PutteJozef Kesecioglu
Nov 17, 2009·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ziying WangFan Yi

❮ Previous
Next ❯

Citations

Oct 24, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Pamela W M KleikersH H H W Schmidt
Apr 6, 2013·Archives of Pharmacal Research·Sangseong Kim, Sun Wook Hwang
Jul 4, 2012·Antioxidants & Redox Signaling·Timo Kahles, Ralf P Brandes
Jul 9, 2013·Cardiovascular Research·Florian LogaJörg W Wegener
Mar 21, 2013·Science Signaling·Arti V ShindeMohamed Trebak
Mar 21, 2013·Science Signaling·Thomas Gudermann, Dirk Steinritz
Nov 23, 2012·BMC Cell Biology·Robert CarrasquilloJohannes Schlöndorff
Aug 21, 2012·World Journal of Biological Chemistry·Francesco MocciaFranco Tanzi
Jan 29, 2014·The Journal of General Physiology·Kyohei ItsukiMasayuki X Mori
Sep 3, 2013·Antioxidants & Redox Signaling·Manish MittalAsrar B Malik
Mar 4, 2014·Advances in Biological Regulation·Gianluca Baldanzi
Jan 18, 2015·Biochimica Et Biophysica Acta·O LindemannA Schwab
Nov 27, 2015·Antioxidants & Redox Signaling·Dmitry Bilan, Vsevolod Belousov
Oct 2, 2015·Pflügers Archiv : European journal of physiology·Monika MalczykOleg Pak
Aug 22, 2015·Redox Biology·Agnes GörlachOlga Krizanova
Nov 5, 2015·Journal of Neuroimmunology·Giuseppe A RamirezAngelo A Manfredi
Oct 10, 2013·British Journal of Pharmacology·Yosuke Kaneko, Arpad Szallasi
May 5, 2012·Biochemical and Biophysical Research Communications·Chang LiaoJundong Jiao
Sep 18, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Lutz Birnbaumer
Dec 19, 2014·Journal of Cellular Physiology·Hermann KalwaAlexander Dietrich
Jan 5, 2014·Antioxidants & Redox Signaling·Sebastian AltenhöferHarald H H W Schmidt
Mar 19, 2013·Biochimica Et Biophysica Acta·Bing-Chen LiuHe-Ping Ma
Apr 22, 2015·Biochemical and Biophysical Research Communications·Bo ZhaoJundong Jiao
Apr 30, 2016·Cell Calcium·Barbora Svobodova, Klaus Groschner
Feb 25, 2014·Journal of Molecular and Cellular Cardiology·Ralf P BrandesKatrin Schröder
Dec 30, 2014·Antioxidants & Redox Signaling·Florian VeitNorbert Weissmann
Jan 13, 2016·American Journal of Respiratory and Critical Care Medicine·Ashish K SharmaVictor E Laubach
Jul 20, 2016·Cell Calcium·Barbora Svobodova, Klaus Groschner
Oct 5, 2016·Scientific Reports·Silvia Cellone TrevelinFernando Queiroz Cunha
Oct 9, 2014·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·P Roxo-Junior, H M L Simão
Feb 6, 2017·Experimental & Molecular Medicine·Luong Dai LyKyu-Sang Park
Jul 10, 2014·Pulmonary Circulation·Patricia C Villalta, Mary I Townsley
Oct 1, 2014·Cells·Alexander DietrichThomas Gudermann
Mar 10, 2018·ChemMedChem·Stephanie HäfnerMichael Schaefer
Aug 30, 2017·Pflügers Archiv : European journal of physiology·Nikolaj NielsenAlbrecht Schwab
Nov 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ana I CasasHarald H H W Schmidt
May 14, 2018·Pflügers Archiv : European journal of physiology·Martina KannlerAlexander Dietrich

❮ Previous
Next ❯

Methods Mentioned

BETA
bronchoalveolar lavage
reverse-transcription PCR
ESR
transgenic

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