Scientific article
Open access

NADPH oxidase 4 deficiency increases tubular cell death during acute ischemic reperfusion injury

Published inScientific Reports, vol. 6, 38598
Publication date2016

NADPH oxidase 4 (NOX4) is highly expressed in kidney proximal tubular cells. NOX4 constitutively produces hydrogen peroxide, which may regulate important pro-survival pathways. Renal ischemia reperfusion injury (IRI) is a classical model mimicking human ischemic acute tubular necrosis. We hypothesized that NOX4 plays a protective role in kidney IRI. In wild type (WT) animals subjected to IRI, NOX4 protein expression increased after 24 hours. NOX4 KO (knock-out) and WT littermates mice were subjected to IRI. NOX4 KO mice displayed decreased renal function and more severe tubular apoptosis, decreased Bcl-2 expression and higher histologic damage scores compared to WT. Activation of NRF2 was decreased in NOX4 KO mice in response to IRI. This was related to decreased KEAP1 oxidation leading to decreased NRF2 stabilization. This resulted in decreased glutathione levels. In vitro silencing of NOX4 in cells showed an enhanced propensity to apoptosis, with reduced expression of NRF2, glutathione content and Bcl-2 expression, similar to cells derived from NOX4 KO mice. Overexpression of a constitutively active form of NRF2 (caNRF2) in NOX4 depleted cells rescued most of this phenotype in cultured cells, implying that NRF2 regulation by ROS issued from NOX4 may play an important role in its anti-apoptotic property.

Citation (ISO format)
NLANDU-KHODO, Stellor et al. NADPH oxidase 4 deficiency increases tubular cell death during acute ischemic reperfusion injury. In: Scientific Reports, 2016, vol. 6, p. 38598. doi: 10.1038/srep38598
Main files (1)
Article (Published version)
ISSN of the journal2045-2322

Technical informations

Creation11/20/2017 9:00:00 PM
First validation11/20/2017 9:00:00 PM
Update time03/15/2023 7:37:21 AM
Status update03/15/2023 7:37:20 AM
Last indexation01/17/2024 1:49:30 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack