| Project/Area Number |
07672018
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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 |
Functional basic dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ISHIKAWA Yasuko The Univ.of Tokushima, Sch.of Dentistry ; Assitant Professor, 歯学部, 助教授 (40144985)
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| Co-Investigator(Kenkyū-buntansha) |
EGUCHI Takafumi The Univ.of Tokushima, Sch.of Dentistry ; Research Associate, 歯学部, 助手 (90263847)
ISHISDA Hajime The Univ.of Tokushima, Sch.of Dentistry ; Professor, 歯学部, 教授 (70028364)
天野 伊知郎 徳島大学, 歯学部, 助手 (20212566)
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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 |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | salivary gland / cell proliferation / isoproterenol / nuclear protein / histone protein / non-histone protein / phosphorylation / aging |
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| Research Abstract |
The regulatory mechanisms of cell proliferation are important in the biochemical manifestation of senescence or cancer. A single injection of isoproterenol (IPR) into rats results in a marked stimulation of DNA synthesis in the salivary glands. The aim of this study was to investigate the mechanism of cell proliferation induced by beta-agonists and the age-dependent alteration of the signal transduction lead to the induction of cell proliferation.
1. Nuclei were isolated from the submandibular glands of rats which had been injected IPR (100mg/kg) intrapeitoneally. Histone(H) and non-histone(nH) proteins were separated from nuclei after the incubation with [gamma-^<32>P] ATP.The level of phosphorylation of nH at 4-week began to increase at 10h after injection of IPR,reaching a maximum at 22h and then returned to the control level. The time after the injection of IPR required to initiate the stimulation of the phosphorylation of nH or the return to the control level increased significantl
… More
y with age.
2. Age-dependent changes in protein kinase activity associated in the choromatin were appeared to correspond to alteration in the phosphorylation of nH.
3. The incorporation of [^3H] thymidine in submandibular gland DNA of 4-week old rats was initiated at 14h after the injection of IPR,reaching a maximum at 22h and returning to the control level at 30h. The time prior to the onset of the DNA synthesis in rat submandibular glands increased during aging.
4. Submandibular glands were obtained from rats which had been injected with [^<32>P] orthophosphate intraperitoneally 2h before IPR-injection. The extracted nuclear proteins were subjected to immunoprecipitation with anti-c-fos antibody, followed by SDS-PAGE.Phosphorylated c-fos was identified by autoradiography. IPR induced the expression of c-fos, but not that of c-jun. The age-dependent changes in c-fosmRNA was regarded as being closely correlated with the alteration of Gs.
In conclusions, IPR stimulates protein kinase associated with the chromatin through signal transduction cascade in which receptor stimulation of adenylate cyclase increases c-fos expression. This kinase regulates the phosphorylation of nH.The delayd onset of phosphorylation of nH play a regulatory role in cell proliferation and cell function during aging. Less
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