| Project/Area Number |
63570525
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Gunma University (1990)
The University of Tokyo (1988-1989) |
|---|
Principal Investigator |
KOJIMA Itaru (1989-1990) Professor, Institute of Endocrinology, Gunma University, 内分泌研究所, 教授 (60143492)
貴田岡 正史 (1988) 東京大学, 医学部, 助手 (20153091)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KITAOKA Masafumi Director, Endocrine Clinic, Showa Hospital, 内分泌代謝科, 医長 (20153091)
小島 至 東京厚生年金病院, 内科, 医長 (60143492)
|
|---|
| Project Period (FY) |
1988 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | Insulin-like Growth Factor / Growth / Calcium / Diacylglycerol / Cell-cycle / G蛋白 / ジアシルグリセロール |
|---|
| Research Abstract |
Insulin-like gowth factor-I (IGF-I) is a potent growth factor which plays a pivotal role in somatic growth. We studied the mechanism of action of IGF-I using Balb/c 3T3 cells as a model system. In these cells, IGF-I promotes cell-cycle progression. In doing so, IGF-I exerts its action in a cell-cycle-dependent manner. Thus, IGF-I promotes cell-cycle progression when quiescent cells are pretreated with platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). We studied the action of IGF-I using IGF-I-responsive cells, which we termed primed competent cells. In these cells, IGF-I induces sustained increase in calcium entry. This is brought about by an activation of IGF-I-sensitive calcium-permeable cation channel. When calcium entry is blocked, IGF-I is not capable of stimulating DNA synthesis. In addition, pharmacological stimulation of calcium entry results in an increase in DNA synthesis. These results let us to propose that calcium entry is an intracellular message of the mitogenic action of IGF-I. It should be mentioned that DNA synthesis is augmented in primed competent cells whereas stimulation of calcium entry does not affect DNA synthesis in quiescent cells. These results indicate that calcium-sensing machinery does not operate in quiescent cells. In addition to stimulation of calcium entry, IGF-I increases diacylglycerol (DAG) in primed competent cells. There are at least three sources of diacylglycerol. First, glycosylphosphatidylinositol, known to be a precursor of insulin-mediator inositolglycan, is hydrolyzed by IGF-I. Second, phosphatidylcholine is hydrolyzed by phospholipase C, and finally, IGF-I stimulates de novo synthesis of diacylglycerol. As a result, IGF-I causes sustained elevation of cellular DAG content. It remains unsolved whether protein kinase C is activated continuously by IGF-I.
|
