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 activity of subcellular renal cortical compartments from 20‐week‐old mice, A) Membranous, B) Mitochondrial, C) Nuclear, D) Cytosolic, *P <0.01 versus WT‐C; †P <0.05 versus WT‐D; ‡P <0.05 versus WT‐C; §P <0.01 versus WT‐D; n =8–10/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig07: PKC activity of subcellular renal cortical compartments from 20‐week‐old mice, A) Membranous, B) Mitochondrial, C) Nuclear, D) Cytosolic, *P <0.01 versus WT‐C; †P <0.05 versus WT‐D; ‡P <0.05 versus WT‐C; §P <0.01 versus WT‐D; n =8–10/group.

Mentions: Activation of PKC has been implicated in the pathogenesis of DN and the induction of mitochondrial ROS in response to glucose has been confirmed in mesangial cells (Kiritoshi et al. 2003); however, the link to subsequent PKC activation has been less well characterized. Thus, we measured PKC activity in specific cellular compartments of the renal cortex from mice with and without expression of Nox4. Diabetes induced an increase in PKC activity in the plasma membrane (Fig. 7A), mitochondria (Fig. 7B), and nucleus (Fig. 7C). This activity was normalized by Nox4 deletion. The PKC activity in the cytosolic fraction was unaffected (Fig. 7D).


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 activity of subcellular renal cortical compartments from 20‐week‐old mice, A) Membranous, B) Mitochondrial, C) Nuclear, D) Cytosolic, *P <0.01 versus WT‐C; †P <0.05 versus WT‐D; ‡P <0.05 versus WT‐C; §P <0.01 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

fig07: PKC activity of subcellular renal cortical compartments from 20‐week‐old mice, A) Membranous, B) Mitochondrial, C) Nuclear, D) Cytosolic, *P <0.01 versus WT‐C; †P <0.05 versus WT‐D; ‡P <0.05 versus WT‐C; §P <0.01 versus WT‐D; n =8–10/group.
Mentions: Activation of PKC has been implicated in the pathogenesis of DN and the induction of mitochondrial ROS in response to glucose has been confirmed in mesangial cells (Kiritoshi et al. 2003); however, the link to subsequent PKC activation has been less well characterized. Thus, we measured PKC activity in specific cellular compartments of the renal cortex from mice with and without expression of Nox4. Diabetes induced an increase in PKC activity in the plasma membrane (Fig. 7A), mitochondria (Fig. 7B), and nucleus (Fig. 7C). This activity was normalized by Nox4 deletion. The PKC activity in the cytosolic fraction was unaffected (Fig. 7D).

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