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Upstream regulators and downstream effectors of NADPH oxidases as novel therapeutic targets for diabetic kidney disease.

Gorin Y, Wauquier F - Mol. Cells (2015)

Bottom Line: Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney.NADPH oxidases of the Nox family, and in particular the homologue Nox4, 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 knowledge related to the understanding of the role of Nox enzymes 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.

ABSTRACT
Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, 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 knowledge related to the understanding of the role of Nox enzymes 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 nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

No MeSH data available.


Related in: MedlinePlus

Structure and molecular organization of the renal Nox NADPH oxidases. 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 homologues predominantly expressed in the kidney, Nox2 (a.k.a. gp91phox), Nox1, Nox4, and Nox5. The regulatory subunits differ from a Nox homologue to another.
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f1-molce-38-4-285: Structure and molecular organization of the renal Nox NADPH oxidases. 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 homologues predominantly expressed in the kidney, Nox2 (a.k.a. gp91phox), Nox1, Nox4, and Nox5. The regulatory subunits differ from a Nox homologue to another.

Mentions: It is important to mention that Nox4 seems to produce a higher hydrogen peroxide to superoxide ratio than Nox1, Nox2 and Nox5. Recent studies strongly suggest that hydrogen peroxide formation occurs through Nox4 third extracytosolic loop (E-loop) and that the structure of the E-loop may obstruct superoxide release as well as provide a source for protons, thus permitting rapid dismutation of superoxide to generate hydrogen peroxide (Takac et al., 2011). Although Nox4 predominantly produces hydrogen peroxide, numerous studies in vascular or renal cells and tissue detected Nox4-dependent superoxide production (Ago et al., 2010; Block et al., 2009; Clempus et al., 2007; Cucoranu et al., 2005; Eid et al., 2009; 2010; Gorin et al., 2005; Kuroda et al., 2005; 2010; Liu et al., 2010; Maalouf et al., 2012; Peshavariya et al., 2007; Shiose et al., 2001). Figure 1 shows the structure and molecular organization of the renal Nox NADPH oxidases.


Upstream regulators and downstream effectors of NADPH oxidases as novel therapeutic targets for diabetic kidney disease.

Gorin Y, Wauquier F - Mol. Cells (2015)

Structure and molecular organization of the renal Nox NADPH oxidases. 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 homologues predominantly expressed in the kidney, Nox2 (a.k.a. gp91phox), Nox1, Nox4, and Nox5. The regulatory subunits differ from a Nox homologue to another.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400302&req=5

f1-molce-38-4-285: Structure and molecular organization of the renal Nox NADPH oxidases. 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 homologues predominantly expressed in the kidney, Nox2 (a.k.a. gp91phox), Nox1, Nox4, and Nox5. The regulatory subunits differ from a Nox homologue to another.
Mentions: It is important to mention that Nox4 seems to produce a higher hydrogen peroxide to superoxide ratio than Nox1, Nox2 and Nox5. Recent studies strongly suggest that hydrogen peroxide formation occurs through Nox4 third extracytosolic loop (E-loop) and that the structure of the E-loop may obstruct superoxide release as well as provide a source for protons, thus permitting rapid dismutation of superoxide to generate hydrogen peroxide (Takac et al., 2011). Although Nox4 predominantly produces hydrogen peroxide, numerous studies in vascular or renal cells and tissue detected Nox4-dependent superoxide production (Ago et al., 2010; Block et al., 2009; Clempus et al., 2007; Cucoranu et al., 2005; Eid et al., 2009; 2010; Gorin et al., 2005; Kuroda et al., 2005; 2010; Liu et al., 2010; Maalouf et al., 2012; Peshavariya et al., 2007; Shiose et al., 2001). Figure 1 shows the structure and molecular organization of the renal Nox NADPH oxidases.

Bottom Line: Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney.NADPH oxidases of the Nox family, and in particular the homologue Nox4, 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 knowledge related to the understanding of the role of Nox enzymes 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.

ABSTRACT
Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, 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 knowledge related to the understanding of the role of Nox enzymes 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 nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

No MeSH data available.


Related in: MedlinePlus