التفاصيل البيبلوغرافية
| العنوان: |
Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice |
| المؤلفون: |
Weissmann, Norbert, Sydykov, Akylbek, Kalwa, Hermann, Storch, Ursula, Fuchs, Beate, Mederos y Schnitzler, Michael, Brandes, Ralf P, Grimminger, Friedrich, Meissner, Marcel, Freichel, Marc, Offermanns, Stefan, Veit, Florian, Pak, Oleg, Krause, Karl-Heinz, Schermuly, Ralph T, Brewer, Alison C, Schmidt, Harald H H W, Seeger, Werner, Shah, Ajay M, Gudermann, Thomas, Ghofrani, Hossein A, Dietrich, Alexander |
| المصدر: |
ISSN: 2041-1723 ; Nature communications, vol. 3 (2012) 649. |
| سنة النشر: |
2012 |
| المجموعة: |
Université de Genève: Archive ouverte UNIGE |
| مصطلحات موضوعية: |
info:eu-repo/classification/ddc/616.07, Animals, Calcium/metabolism, Diacylglycerol Kinase/metabolism, Edema/pathology/therapy, Endothelial Cells/cytology, Gene Deletion, Lung/pathology, Membrane Glycoproteins/genetics, Mice, Inbred C57BL, Transgenic, Models, Biological, NADPH Oxidase/genetics, Permeability, Phospholipase C gamma/metabolism, Reactive Oxygen Species, Reperfusion Injury, TRPC Cation Channels/genetics, Time Factors |
| الوصف: |
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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/22337127; https://archive-ouverte.unige.ch/unige:32460; unige:32460 |
| الاتاحة: |
https://archive-ouverte.unige.ch/unige:32460 |
| Rights: |
info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.1417F756 |
| قاعدة البيانات: |
BASE |