TY  - JOUR
A1  - Rezende Felipe, Flávia Figueiredo de
A1  - Moll, Franziska
A1  - Walter, Maria
A1  - Helfinger, Valeska
A1  - Hahner, Fabian
A1  - Janetzko, Patrick
A1  - Ringel, Christian
A1  - Weigert, Andreas
A1  - Fleming, Ingrid
A1  - Weißmann, Norbert
A1  - Künne, Carsten Tobias
A1  - Looso, Mario
A1  - Rieger, Michael A.
A1  - Nawroth, Peter
A1  - Fleming, Thomas
A1  - Brandes, Ralf
A1  - Schröder, Katrin
T1  - The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice
T2  - Redox Biology
N2  - 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.
KW  - NADPH oxidase
KW  - NoxO1
KW  - Nox1
KW  - p47phox
KW  - Superoxide
KW  - Reactive oxygen species
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46382
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-463829
SN  - 2213-2317
N1  - Under a Creative Commons license
VL  - 15
SP  - 12
EP  - 21
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -