Nox-4 and progressive kidney disease.
OBJECTIVE
Nox-4 is a member of the NADPH oxidase (Nox) family of enzymes implicated in reactive oxygen species generation. Nox-4 is distributed in many tissues; however, its physiological functions remain poorly understood. In contrast to other Nox isoforms, it is unique in that it produces large amounts of hydrogen peroxide constitutively and does not require other cytosolic oxidase components for its activation. This review highlights the recent developments in Nox-4 research and progressive kidney disease as well as the potential of new Nox-4 inhibitors to reduce renal damage.


RESULTS
Recently, Nox-4 was shown to be implicated in kidney diseases such as diabetic nephropathy. Nox-4 has been identified as playing a role in damage to the kidney induced by hyperglycaemia and other major pathways of renal damage, including advanced glycation end-products, the renin-angiotensin system, TGF-β and protein kinase C.


CONCLUSIONS
The role of Nox-4 as a target for renoprotection remains controversial, although recent positive preclinical data have stimulated increased interest in inhibiting the enzyme in clinical trials of renal disease.
aDiabetes Complications Division, Baker IDI Heart & Diabetes Institute, JDRF Danielle Alberti Memorial Centre for Diabetic Complications bDepartment of Medicine, Austin and Northern Clinical Schools, University of Melbourne cDepartment of Medicine, Central Clinical School, Monash University, AMREP Precinct, Melbourne, Victoria, Australia.
Vicki
V
Thallas-Bonke
Karin A M
KA
Jandeleit-Dahm
Mark E
ME
Cooper
D000818:Animals; D003928:Diabetic Nephropathies / Q000201:enzymology; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000201:enzymology*
D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human