Basic fibroblast growth factor (bFGF) requires heparan sulfate (HS) that contains bFGF-binding domains for regulating gllomerular cell apoptosis (AP)
| Project/Area Number |
07671247
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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 | Nagoya University |
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Principal Investigator |
SHINZATO Toru School of Medicine Nagoya University, Assistant Professor, 医学部, 助手 (00252247)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Hiroyuki School of Medicine, Nagoya University Staff, 分子医科学研究所, 医員
KIMATA Koji Aichi Medical University Institute for Molecular Science of Medicine, 分子医科学研究所, 教授 (10022641)
ISOBE Ken-ichi The National Sanatorium Chubu Hospital, National Institute for Longevity Science, 長寿医療研究センター, 老化機構研究部長 (20151441)
MAEDA Kenji School of Medicine Nagoya University, Professor, 医学部, 教授 (90023853)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | heparansulfate / apoptosis / mesangial cells / basic fibroblast growth factor / ヘパリン |
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| Research Abstract |
Basic FGF can function as a survival factor in certain cell lineages. It requires a cofactor, HS or heparin (HP), for the activation of signal-transducing bFGF receptors. HS/HP are heterogeneous carbohydrates. We hypothesized that specific interaction between bFGF and bFGF-binding domains of HS might optimize bFGF's ability of regulating AP induced in glomerular cells. To test this hypothesis, we compared the effects of various forms of glycosaminoglycans (GAG). Two types of Engelbreth-Holm-Swarm tumor HS with respect to the affinity for bFGF were fractionated : the bound and unbound HS.The bound HS were enriched in IdoA(2SO4)-GlcNSO3 units. In order to trigger AP,a) isolated glomeruli from Wistar rats were incubated with Trimeresurus flavoviridis vebom, or b) rat mesangial cells in culture were deprived growth factors. The bound HS,te unbound HS,or either one of the other forms of GAG (HP,hyaluronate, chondroitin sulfate, dermatan sulfate and keratan sulfate) was added to the culture media at various concentrations (4ng/ml-40mug/ml) with bFGF (0.5-5.0ng/ml) in the presence or absence of cycloheximide (250muM). To detect DNA cleavage and subsequent nuclear changes typical of AP,DNA electrophoresis, light microscopic examination and TdT-mediated dUTP-biotin nick and labeling (TUNEL) were conducted. AP of the isolated glomeruli and cultured mesangial cells were successfully introduced. To rescue AP,5.0ng/ml of bFGF required HS or HS (5.0mug/ml or more as uronate) that contains bFGF-binding portions. Cycloheximide treatment inhibited this activity of bFGF.Other GAG did not give such regulatory effects at the same concentration.
Conclusion : The results suggest that the bFGF-binding portions help regulate AP.These studies may contribute toward establishing a framework for the molecular design of carbohydrates capable of optimizing bFGF activity.
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Research Products
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