Limits...
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.


Related in: MedlinePlus

PKC‐α expression at 20 weeks A) Membranous fraction and B) Mitochondrial fraction of renal cortex by ELISA. C) Computer‐aided analysis of immunohistochemical staining of renal cortical PKC‐α expressed as percent area and D) Representative photomicrographs of PKC‐α immunostaining in renal cortex of kidney (×400 magnification), (i) WT‐C; (ii) WT‐D, (iii) Nox4‐KO‐C; (iv) Nox4‐KO‐D. *P <0.01 versus WT‐C; †P <0.01 versus WT‐D; ‡P <0.05 versus WT‐D, §P <0.001 versus WT‐D, n =8–10/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4255803&req=5

fig08: PKC‐α expression at 20 weeks A) Membranous fraction and B) Mitochondrial fraction of renal cortex by ELISA. C) Computer‐aided analysis of immunohistochemical staining of renal cortical PKC‐α expressed as percent area and D) Representative photomicrographs of PKC‐α immunostaining in renal cortex of kidney (×400 magnification), (i) WT‐C; (ii) WT‐D, (iii) Nox4‐KO‐C; (iv) Nox4‐KO‐D. *P <0.01 versus WT‐C; †P <0.01 versus WT‐D; ‡P <0.05 versus WT‐D, §P <0.001 versus WT‐D, n =8–10/group.

Mentions: Next, the key canonical isoforms of PKC were determined. PKC‐α content of the plasma membrane (Fig. 8A) and the mitochondria (Fig. 8B) was increased in diabetic mice, and this increase was attenuated by Nox4 deletion. An overall assessment of PKC‐α in the renal cortex by immunohistochemical staining demonstrated an increase in the WT‐D mice compared to the WT‐C with a significant decrease in the Nox4 KO‐D animals (Fig. 8C and D). Similar results were observed with PKC‐β1, in which an increase in protein expression was found in the WT‐D group with a significant reduction in the KO‐D animals (Fig. 9A and B).


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)

PKC‐α expression at 20 weeks A) Membranous fraction and B) Mitochondrial fraction of renal cortex by ELISA. C) Computer‐aided analysis of immunohistochemical staining of renal cortical PKC‐α expressed as percent area and D) Representative photomicrographs of PKC‐α immunostaining in renal cortex of kidney (×400 magnification), (i) WT‐C; (ii) WT‐D, (iii) Nox4‐KO‐C; (iv) Nox4‐KO‐D. *P <0.01 versus WT‐C; †P <0.01 versus WT‐D; ‡P <0.05 versus WT‐D, §P <0.001 versus WT‐D, n =8–10/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig08: PKC‐α expression at 20 weeks A) Membranous fraction and B) Mitochondrial fraction of renal cortex by ELISA. C) Computer‐aided analysis of immunohistochemical staining of renal cortical PKC‐α expressed as percent area and D) Representative photomicrographs of PKC‐α immunostaining in renal cortex of kidney (×400 magnification), (i) WT‐C; (ii) WT‐D, (iii) Nox4‐KO‐C; (iv) Nox4‐KO‐D. *P <0.01 versus WT‐C; †P <0.01 versus WT‐D; ‡P <0.05 versus WT‐D, §P <0.001 versus WT‐D, n =8–10/group.
Mentions: Next, the key canonical isoforms of PKC were determined. PKC‐α content of the plasma membrane (Fig. 8A) and the mitochondria (Fig. 8B) was increased in diabetic mice, and this increase was attenuated by Nox4 deletion. An overall assessment of PKC‐α in the renal cortex by immunohistochemical staining demonstrated an increase in the WT‐D mice compared to the WT‐C with a significant decrease in the Nox4 KO‐D animals (Fig. 8C and D). Similar results were observed with PKC‐β1, in which an increase in protein expression was found in the WT‐D group with a significant reduction in the KO‐D animals (Fig. 9A and B).

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