The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice
| Autor: | 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 |
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| Jazyk: | němčina |
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Redox Biol. 15, 12-21 (2018) Redox Biology, Vol 15, Iss C, Pp 12-21 (2018) Redox Biology |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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