2004 Fiscal Year Final Research Report Summary
Prevention of glomerulosclerosis through the regulation of isoprostane pathway
| Project/Area Number |
15590873
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kagawa Prefctural College of Health Sciences (2004)
Kagawa Prefectural College of Health science (2003) |
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Principal Investigator |
YUASA Shigekazu Faculty of Health Sciences, Dept of MedicalTechnology, Professor, 保健医療学部・臨床検査学科, 教授 (60174827)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUNAGA Megumu Kagawa University, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (40283775)
KIYOMOTO Hideyasu Kagawa University, Faculty of Medicine, Research Associate, 医学部, 助手 (00304585)
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| Project Period (FY) |
2003 – 2004
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| Keywords | glomerulosclerosis / renal failure / hemodialysis / isoprostane / phosphodiesterase / phosphodiesterase (PDE) |
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| Research Abstract |
Glomerulosclerosis has been widely recognized in the kidney of end-stage renal failure patients requiring renal replacement therapy. Recently, it has been postulated that oxidative stress may play a role in the pathogenesis of glomerulosclerosis. In this study, we examined the role of oxidative stress in the progression of giomerulosclerosis using oxidative stress-generated isoprostane.
(1)Interferon y significantly increased the production of superoxide anion in cultured human mesangial cells by enhancing the NADPH oxidase activity via the activation of S1AT pathway.
(2)In Dahl salt-sensitive rats, tempol, which possess the activity similar to superoxide dismutase, and angiotensin AT1 receptor blockade significantly inhibited the increase of blood pressure and urinary protein excretion, and ameliorated progressive sclerotic glomerular changes.
(3)Specific distribution of phosphodiesterase 10A mRNA, which catalyzes the hydrolysis of cyclic nucleotide second messengers, was observed in glomerular epithelial cells in rat kidney.
(4)Chronic hemodialysis patients are exposed to more oxidative stress through dialysis itself and this oxidative stress decreased by the use of biocompatible vitamin E coated dialysis membrane or vitamin E administration.
These results demonstrate that oxidative stress plays an important role in the progression of glomerulosclerosis. Future studies are required for evaluating the relation between phosphodiesterase activity and oxidative stress in the pathogenesis of glomerulosclerosis.
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