The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice
| العنوان: | The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice |
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| المؤلفون: | Michael A. Rieger, Mario Looso, Norbert Weissmann, Maria Walter, Franziska Moll, Peter P. Nawroth, Valeska Helfinger, Fabian Hahner, Flávia Rezende, Patrick Janetzko, Ingrid Fleming, Katrin Schröder, Christian Ringel, Ralf P. Brandes, Thomas Fleming, Andreas Weigert, Carsten Kuenne |
| المصدر: | Redox Biol. 15, 12-21 (2018) Redox Biology, Vol 15, Iss C, Pp 12-21 (2018) Redox Biology |
| بيانات النشر: | Elsevier Science Bv, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Chemokine, medicine.medical_treatment, Clinical Biochemistry, Gene Expression, Biochemistry, Mice, Gene expression, Interferon gamma, Lymphocytes, lcsh:QH301-705.5, Nadph Oxidase, Noxo1, Nox1, P47phox, Superoxide, Reactive Oxygen Species, Aorta, Mice, Knockout, lcsh:R5-920, NADPH oxidase, biology, Chemistry, Nox, NADPH oxidase, Cell biology, Cytokine, CBA, Cytometric Bead Assay, NOX1, Knockout mouse, PMA, Phorbol Myristate Acetate, lcsh:Medicine (General), NoxO1, medicine.drug, Protein Binding, Research Paper, Gpx3, Glutathione peroxidase 3, Antigen presentation, eNOS, endothelial Nitric Oxide Synthase, Diabetes Mellitus, Experimental, 03 medical and health sciences, medicine, Animals, Humans, ddc:610, MACE, Massive Analysis of cDNA ends, Adaptor Proteins, Signal Transducing, Organic Chemistry, Endothelial Cells, NADPH Oxidases, Proteins, p47phox, STZ, Streptozotocin, 030104 developmental biology, lcsh:Biology (General), biology.protein, SMCs, Smooth Muscle Cells, Reactive oxygen species, NADP, IFNɣ, Interferon gamma, ROS, Reactive Oxygen Species |
| الوصف: | Aim NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes. Results In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice. Innovation and conclusion ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response. Graphical abstract fx1 |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | German |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8a2b66fb96b704096740836bd937bf3Test https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=52450Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b8a2b66fb96b704096740836bd937bf3 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |