Activation of protein kinase C-δ and C-ε by oxidative stress in early diabetic rat kidney

H. Ha, M. R. Yu, Jin Choi Yoon Jin Choi, Bahl Lee Hi Bahl Lee

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61 Scopus citations

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-α, PKC-βI, PKC-βII, PKC-δ, and PKC-ε and DAG-independent PKC-ζ 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-δ and PKC-ε content increased 47% and 57% above control, and membrane PKC-βI content decreased to 67% of control. The membrane-associated PKC-α, PKC-βII, and PKC-ζ content were not influenced. Total PKC-δ (163%) and PKC-ε (157%) increased significantly in diabetic tubules. Taurine prevented proteinuria and effectively inhibited alterations in PKC-δ and PKC-ε of diabetic glomeruli and tubules at dose-inhibiting lipid peroxidation but not hyperglycemia. These data suggest that PKC-δ and PKC-ε are sensitively activated by hyperglycemia-induced oxidative stress in diabetic rat kidney.

Original languageEnglish
Pages (from-to)S204-S207
JournalAmerican Journal of Kidney Diseases
Volume38
Issue number4 SUPPL. 1
DOIs
StatePublished - 2001

Keywords

  • Diabetic nephropathy
  • Oxidative stress
  • Protein kinase C
  • Streptozotocin
  • Taurine

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