| Project/Area Number |
02454239
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KAWAKAMI Yoshikazu (1991-1992) FIRST DEPARTMENT OF MEDICINE,SCHOOL OF MEDICINE,HOKKAIDO UNIVERSITY. PROFESSOR, 医学部, 教授 (10001877)
長田 博 (1990) 北海道大学, 医学部附属病院, 講師 (30164437)
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| Co-Investigator(Kenkyū-buntansha) |
川上 義和 北海道大学, 医学部, 教授 (10001877)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1990: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | PLATELET / ENDOTHELIAL CELL / GLUTATHIONE / ARDS / 呼吸不全 / DIC / プロテインC / PAIー1 / GpIIb / IIIa / 白血球 / TP80 |
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| Research Abstract |
The defense system of aortic endothelial cells against oxidative stress was studied in alloxan-induced diabetic rabbits,and the effect of insulin on the antioxidant activities was estimated. Endothelial cells were prepared from 10 diabetic rabbits, 18 diabetic rabbits treated with insulin, and 10 age-matched controls after 17 days of diabetes. These cells were used for the estimation of glutathione (GSH) levels and its related enzyme activities. The antioxidant activities in these endothelial cells from diabetic rabbits were compared with those from control subjects. The concentration of GSH decreased in diabetic rabbits (1.6*0.2 nmol/mg protein [mean*SD] nu 3.7*0.6nmol/mg protein). Decreases in the activities of Cu. Zn-superoxide dismutase(Cu,Zn-SOD)(62.7*11.0U/mg protein nu 172.9*20.2U/mg protein),catalase(7.6*2.1U/mg protein v 12.3*3.2 U/mg protein), and GSH peroxidase (134.0*27.0 mU/mg protein v 179.1*26.2 mU/mg protein) were observed. The activities of other GSH-related enzymes su
… More
ch as GSH S-transferase or GSH reductase did not change in endothelial cells from diabetic rabbits. Most of these antioxidant activities were prevented when diabetic rabbits were treated with insulin (1 to 2 U/kg/d). These antioxidant activities were also determined in the diabetic liver and kidney. Similar decreases in the cellular defense activities and prevention of the decrease in activities by insulin were observed in the diabetic liver, while these antioxidant enzyme activities in the kidney were resistant to diabetic conditions. The activity of a SGSH-synthesizing enzyme, gamma-glutamylcysteine synthetase,decreased in diabetic liver,which may account for the decrease in the concentration of GSH. These results indicate that GSH and its related enzyme activities are impaired in endothelial cells from diabetic rabbits as observed in the liver,and that these impairments are prevented by treatment with insulin. The decrease in antioxidant activity may have significance in the spectrum of pathology associated with diabetes mellitus. Less
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