2000 Fiscal Year Final Research Report Summary
The role of apoptosis in cisplatin-induced acute renal failure.
| Project/Area Number |
10670993
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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 | Hamamatsu University School of Medicine. |
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Principal Investigator |
HISHIDA Akira Hamamatsu University School of Medicine, Medicine, Professor, 医学部, 教授 (70111812)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Akihiko Hamamatsu University School of Medicine, University Hospital, Instructor, 医学部・付属病院, 助手 (60324357)
FUJIGAKI Yoshihide Hamamatsu University School of Medicine, Medicine, Instructor, 医学部, 助手 (20283351)
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| Project Period (FY) |
1998 – 2000
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| Keywords | apoptosis / cisplatin / acute renal failure / p21 / p53 / cell cycle / DNA repair |
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| Research Abstract |
It is well known that apoptotic cell death is induced in nephrotoxic acute renal failure. However, the roles of apoptosis in the development of acute renal failure have not been studied. In this study the degree of apoptosis in cisplatin-induced acute renal failure was evaluated before and after the modification of cisplatin-induced tubular damage by the administration of dimethylthiourea or glycine, or by the pretreatment with other nephrotoxic substance ( uranyl acetate), all of these were reported to attenuate the tubular cell damage. A significant positive correlation was found between the tubular damage score and the number of apoptotic cell death evaluated by TUNEL method. The increase in TUNEL positive cells in the early phase of acute renal failure was associated with the increases in proliferating cell nuclear antigen (PCNA), p53 and p21 (an inhibitor of cyclin-dependent kinase inhibitor). The increase in PCNA was not associated with the increase in the BrdU incorporation which is a marker of cell proliferation, suggesting that the increase in PCNA positive cells does not reflect the enhanced cell proliferation but reflect the enhanced DNA repair. These findings may suggest that apoptotic cell death play an important role in the development of tubular damage in cisplatin-induced acute renal failure and may indicate that the tubular cells damaged by cisplatin induces the p53-mediated overexpression of p21 and stops the cell cycle at G1/S phase, providing the time for DNA repair. The cells which were not repaired may undergo apoptosis and contribute to tubular damage in cisplatin-induced acute renal failure.
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