The NADPH organizers NoxO1 and p47phox are mediators of diabetes-induced vascular dysfunction.


eMediNexus    19 December 2017

The aim of a new study published in Redox Biology was to determine whether Nox homologues exhibit crosstalk at the activity level. In this experiment, 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. It was observed that in the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells. On the other hand, 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. In addition, deletion of any of the two subunits prevented diabetes-induced vascular dysfunction. Moreover, mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Meanwhile, deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. Whereas, 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. Hence, it was concluded that ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. It was stated that NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype; in contrast, p47phox deletion elicited a hyper-inflammatory response.

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