Evalution of oxidative stress in diabetic animals by in vivo electron spin resonance measurement--role of protein kinase C.
Enhanced oxidative stress may be an important contributor to the pathogenesis of diabetic vascular complication. Although hyperglycemia-induced oxidative stress in diabetes has been well documented, exact source in vivo remains to be elucidated. Here we report a role of protein kinase C (PKC) in oxidative stress in diabetic animals using a technique of in vivo electron spin resonance (ESR) measurement that has been developed for direct and non-invasive analysis of free radical generation in living animals. First, using this measurement, we confirmed that streptozotocin-induced diabetic rats which showed a significant increase in free radical generation, which was restored by alpha-tocopherol treatment. Treatment of PKC inhibitor CGP41251 (50 mg/kg) or NAD(P)H oxidase inhibitor apocynin (5 mg/kg) restored the increased free radical generation in those diabetic animals. In conclusion, the present study provided the evidence that PKC-dependent activation of vascular NAD(P)H oxidase may be a major source in enhanced oxidative stress in diabetes in vivo. This may contribute to the pathogenesis of diabetic vascular complications.
Sonta
Toshiyo
T
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Inoguchi
Toyoshi
T
Tsubouchi
Hirotaka
H
Sekiguchi
Naotaka
N
Kobayashi
Kunihisa
K
Matsumoto
Shingo
S
Utsumi
Hideo
H
Nawata
Hajime
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D018384:Oxidative Stress / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013113:Spin Labels
D013113:Spin Labels; D011493:Protein Kinase C