Activation of Protein Kinase C-Delta and C-Epsilon by Oxidative Stress in Early Diabetic Rat Kidney

Am J Kidney Dis. 2001 Oct;38(4 Suppl 1):S204-7. doi: 10.1053/ajkd.2001.27446.

Abstract

Hyperglycemia-induced oxidative stress and protein kinase C (PKC) activation are implicated in the development and progression of diabetic nephropathy. Although PKC activation under hyperglycemia largely is related to an increase in de novo synthesis of diacylglycerol (DAG), activation of PKC can be regulated sensitively by oxidative stress. We investigated the expression and translocation of PKC isoforms in streptozotocin (STZ)-induced diabetic rat glomeruli and tubules and the effect of an antioxidant taurine. Experimental diabetes was induced by intravenous injection of 50 mg/kg of STZ. Two days after STZ, diabetic rats were assigned to one of two groups: untreated or treated with taurine 1% in drinking water. Four weeks after STZ, PKC isoforms were measured by Western blot analysis in the isolated glomeruli and tubules. DAG-dependent PKC isoforms PKC-alpha, PKC-betaI, PKC-betaII, PKC-delta, and PKC-epsilon and DAG-independent PKC-zeta all were detected in control rat glomeruli and tubules. Streptozotocin increased plasma glucose from 167 +/- 11 mg/dL to 575 +/- 35 mg/dL (n = 9, P < 0.01) and lipid peroxidation from 1.9 +/- 0.2 nmol/mL to 4.2 +/- 0.6 nmol/mL (P < 0.05) and induced proteinuria. In diabetic glomeruli, membrane-associated PKC-delta and PKC-epsilon content increased 47% and 57% above control, and membrane PKC-betaI content decreased to 67% of control. The membrane-associated PKC-alpha, PKC-betaII, and PKC-zeta content were not influenced. Total PKC-delta (163%) and PKC-epsilon (157%) increased significantly in diabetic tubules. Taurine prevented proteinuria and effectively inhibited alterations in PKC-delta and PKC-epsilon of diabetic glomeruli and tubules at dose-inhibiting lipid peroxidation but not hyperglycemia. These data suggest that PKC-delta and PKC-epsilon are sensitively activated by hyperglycemia-induced oxidative stress in diabetic rat kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus / chemically induced
  • Diabetes Mellitus / physiopathology*
  • Disease Progression
  • Enzyme Activation
  • Hyperglycemia / physiopathology
  • Isoenzymes / metabolism*
  • Kidney / physiopathology*
  • Kidney Tubules / enzymology
  • Male
  • Oxidative Stress*
  • Protein Kinase C / metabolism*
  • Protein Kinase C-delta
  • Protein Kinase C-epsilon
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin

Substances

  • Isoenzymes
  • Streptozocin
  • Prkcd protein, rat
  • Prkce protein, rat
  • Protein Kinase C
  • Protein Kinase C-delta
  • Protein Kinase C-epsilon