| Project/Area Number |
10832007
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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 |
老化(加齢)
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| Research Institution | FUKUSHIMA MEDICAL UNIVERSITY |
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Principal Investigator |
HOMMA Miwako k. Fukushima Medical University, Biomolecular Sciences, Research Associate, 医学部, 助手 (40192538)
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| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | SENESCENT / SIGNALTRANSDUCTION / INOSITOL PHOSPHOLIPIDS / RNA EDITING / イノシトールリン脂質代謝 / RNAエディティング |
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| Research Abstract |
Human diploid fibroblast cells lose replicative capacity in culture after a specific number of population doublings (PDL) and have been widely used as an in vitro model of aging. Senescence is marked by several changes, including decreaed efficiency of growing in response to several growth factors. We examine here the changes of cellular signal transduction system stimulated by a growth factor, PDGF used normal human fibroblast cell line, TIG-3, Young HF cells showed an increased production of inositol trisphophate and diacylglycerol after the treatment with PDGF caused by enhanced inositol phospholipid metabolism. On the contrary, in senescent HF cells showed decreased production of these second messengers. Amounts of PDGF receptor and phospholipase C enzyme, which catalyzes PIP2 cleavage, were almost the same between young and senescent HF cells. We next examined the editing of mRNA transcripts, which is an important mechanism for augumenting the flexibility of eukaryotic gene expression. RNA coding the alpha subtype of PDGF receptor undergoes a post-translational modification in which a genomically encoded adenosine is represented as a guanine in the cDNA of senescent cells. We suggest that the failure to respond to growth stimuli in senescent cells may account for the inability of these cells to transduce the signal following the binding of PDGF to the receptor, which in turn may block the activation of signaling cascade required for entry into cell division cycle.
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