TY - JOUR
T1 - Activation of protein kinase C-δ and C-ε by oxidative stress in early diabetic rat kidney
AU - Ha, H.
AU - Yu, M. R.
AU - Yoon Jin Choi, Jin Choi
AU - Hi Bahl Lee, Bahl Lee
N1 - Funding Information:
Supported by a grant from Korea Science and Engineering Foundation (KOSEF 986-0700-003-2).
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Diabetic nephropathy
KW - Oxidative stress
KW - Protein kinase C
KW - Streptozotocin
KW - Taurine
UR - http://www.scopus.com/inward/record.url?scp=0034817425&partnerID=8YFLogxK
U2 - 10.1053/ajkd.2001.27446
DO - 10.1053/ajkd.2001.27446
M3 - Article
C2 - 11576956
AN - SCOPUS:0034817425
SN - 0272-6386
VL - 38
SP - S204-S207
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 4 SUPPL. 1
ER -