Nox4 NADPH oxidase mediates peroxynitrite-dependent uncoupling of endothelial nitric-oxide synthase and fibronectin expression in response to angiotensin II: Role of mitochondrial reactive oxygen species

Doug Yoon Lee, Fabien Wauquier, Assaad A. Eid, Linda J. Roman, Goutam Ghosh-Choudhury, Khaled Khazim, Karen Block, Yves Gorin

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Background:Oxidative stress is critical for the fibrotic response of mesangial cells (MCs) to angiotensin II. Results:Nox4- and mitochondrial reactive oxygen species (ROS)-dependent endothelial nitric-oxide synthase (eNOS) uncoupling led to fibronectin accumulation in MCs stimulated by angiotensin II. Conclusion:The Nox4/mitochondrial ROS/eNOS pathway mediates angiotensin II-induced MC injury. Significance:Targeting Nox4 and mitochondrial ROS is a promising therapeutic approach.

Original languageEnglish
Pages (from-to)28668-28686
Number of pages19
JournalJournal of Biological Chemistry
Volume288
Issue number40
DOIs
StatePublished - 4 Oct 2013
Externally publishedYes

Funding

FundersFunder number
National Institutes of HealthRO1 DK 079996, RO1 DK 50190, RO1 CA 131272
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK079996

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