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Nox-4 deletion reduces oxidative stress and injury by PKC-α-associated mechanisms in diabetic nephropathy.

Thallas-Bonke V, Jha JC, Gray SP, Barit D, Haller H, Schmidt HH, Coughlan MT, Cooper ME, Forbes JM, Jandeleit-Dahm KA - Physiol Rep (2014)

Bottom Line: Nox4 deletion attenuated diabetes-associated increases in albuminuria, glomerulosclerosis, and extracellular matrix accumulation.Lack of Nox4 resulted in a decrease in diabetes-induced renal cortical ROS derived from the mitochondria and the cytosol, urinary isoprostanes, and PKC activity.Downregulation of the PKC pathway was observed in tandem with reduced expression of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1 and restoration of the podocyte slit pore protein nephrin.

View Article: PubMed Central - PubMed

Affiliation: Diabetes Complications Division, Baker IDI Heart & Diabetes Institute, JDRF Danielle Alberti Memorial Centre for Diabetic Complications, Melbourne, Victoria, Australia Department of Medicine, Austin and Northern Clinical Schools, University of Melbourne, Melbourne, Victoria, Australia.

No MeSH data available.


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Speculative schema for the involvement of Nox4 and PKC in diabetic nephropathy.
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fig10: Speculative schema for the involvement of Nox4 and PKC in diabetic nephropathy.

Mentions: These studies have focused on the role of deletion of Nox4 on the regulation of the PKC pathway in diabetic kidney disease (Fig. 10). We have shown for the first time the renoprotective effects of global deletion of Nox4 in a model of streptozotocin‐induced diabetes. This resulted in improved renal injury with significant reduction in albuminuria, GSI, mitochondrial and cytosolic sources of superoxide, a decrease in urinary isoprostanes, and expression of glomerular collagen IV and fibronectin in association with reduced expression of the PKC‐α and ‐β isoforms. Previous studies in Nox4 knockout mice have produced conflicting data (Babelova et al. 2012), with our recent study showing a renoprotective effect of Nox4 deletion in a different model (Jha et al. 2014). However, the mechanisms whereby Nox4 appears to afford renoprotection and in particular the link to PKC remain inadequately examined and need further evaluation.


Nox-4 deletion reduces oxidative stress and injury by PKC-α-associated mechanisms in diabetic nephropathy.

Thallas-Bonke V, Jha JC, Gray SP, Barit D, Haller H, Schmidt HH, Coughlan MT, Cooper ME, Forbes JM, Jandeleit-Dahm KA - Physiol Rep (2014)

Speculative schema for the involvement of Nox4 and PKC in diabetic nephropathy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255803&req=5

fig10: Speculative schema for the involvement of Nox4 and PKC in diabetic nephropathy.
Mentions: These studies have focused on the role of deletion of Nox4 on the regulation of the PKC pathway in diabetic kidney disease (Fig. 10). We have shown for the first time the renoprotective effects of global deletion of Nox4 in a model of streptozotocin‐induced diabetes. This resulted in improved renal injury with significant reduction in albuminuria, GSI, mitochondrial and cytosolic sources of superoxide, a decrease in urinary isoprostanes, and expression of glomerular collagen IV and fibronectin in association with reduced expression of the PKC‐α and ‐β isoforms. Previous studies in Nox4 knockout mice have produced conflicting data (Babelova et al. 2012), with our recent study showing a renoprotective effect of Nox4 deletion in a different model (Jha et al. 2014). However, the mechanisms whereby Nox4 appears to afford renoprotection and in particular the link to PKC remain inadequately examined and need further evaluation.

Bottom Line: Nox4 deletion attenuated diabetes-associated increases in albuminuria, glomerulosclerosis, and extracellular matrix accumulation.Lack of Nox4 resulted in a decrease in diabetes-induced renal cortical ROS derived from the mitochondria and the cytosol, urinary isoprostanes, and PKC activity.Downregulation of the PKC pathway was observed in tandem with reduced expression of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1 and restoration of the podocyte slit pore protein nephrin.

View Article: PubMed Central - PubMed

Affiliation: Diabetes Complications Division, Baker IDI Heart & Diabetes Institute, JDRF Danielle Alberti Memorial Centre for Diabetic Complications, Melbourne, Victoria, Australia Department of Medicine, Austin and Northern Clinical Schools, University of Melbourne, Melbourne, Victoria, Australia.

No MeSH data available.


Related in: MedlinePlus