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Review
. 2013 Aug:61:130-42.
doi: 10.1016/j.freeradbiomed.2013.03.014. Epub 2013 Mar 23.

Nox4 and diabetic nephropathy: with a friend like this, who needs enemies?

Yves Gorin  1 , Karen Block  2
Affiliations
Review

Nox4 and diabetic nephropathy: with a friend like this, who needs enemies?

Yves Gorin et al. Free Radic Biol Med. 2013 Aug.

Abstract

Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, a complication of diabetes in the kidney. NADPH oxidases of the Nox family are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current understanding of the roles of Nox catalytic and regulatory subunits in the processes that control mesangial cell, podocyte, and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-β. The role of the Nox isoform Nox4 in the redox processes that alter renal biology in diabetes is highlighted.

Keywords: Diabetic complications; Diabetic nephropathy; Free radicals; Glomerular cell injury; Hyperglycemia; NADPH oxidases of the Nox family; Nox4; Oxidative stress; Reactive oxygen species; Tubulointerstitial cell injury.

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Figures

Figure 1
Figure 1
Structure and molecular organization of the renal NADPH oxidases of the Nox family. The top right left panel illustrates the topology of and the enzymatic reaction catalyzed by the Nox enzymes. The other panels represent the molecular structure of the Nox oxidase isoforms predominantly expressed in the kidney, Nox2 (a.k.a. gp91phox), Nox1, and Nox4. The regulatory subunits differ from a Nox isoform to another.
Figure 2
Figure 2
Nox-dependent signaling pathways implicated in glomerular mesangial cell injury triggered by diabetic stimuli. See text for detail.
Figure 3
Figure 3
Nox-dependent signaling pathways implicated in podocyte injury triggered by diabetic stimuli. See text for detail.
Figure 4
Figure 4
Nox-dependent signaling pathways implicated in tubular cell injury triggered by diabetic stimuli. See text for detail.
See this image and copyright information in PMC

References

    1. Hakim FA, Pflueger A. Role of oxidative stress in diabetic kidney disease. Medical science monitor : international medical journal of experimental and clinical research. 2010;16:RA37–48. - PubMed
    1. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40:405–412. - PubMed
    1. Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes. 2008;57:1446–1454. - PubMed
    1. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circulation research. 2010;107:1058–1070. - PMC - PubMed
    1. Hinokio Y, Suzuki S, Hirai M, Chiba M, Hirai A, Toyota T. Oxidative DNA damage in diabetes mellitus: its association with diabetic complications. Diabetologia. 1999;42:995–998. - PubMed

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