| Project/Area Number |
16591101
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | Kagawa University |
|---|
Principal Investigator |
KUBOTA Yasuo Kagawa University, Falucity of Medicine, Professor, 医学部, 教授 (10126047)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Junsuke Kagawa University, Falucity of Medicine, Assistant Professor, 医学部, 助教授 (20346638)
KOSAKA Hiroaki Kagawa University, Falucity of Medicine, Professor, 医学部, 教授 (60158897)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | apoptosis / platelet / lipid / vascular endothelial cell / S1P / 血管新生 / 過酸化水素 / カスパーゼ / 血管成熟 / VEGF / PDGF |
|---|
| Research Abstract |
Sphingosine 1-phosphate (S1P) is a platelet-derived lipid mediator that modulates a wide array of vascular functions, including regulation of blood pressure, cellular proliferation and angiogenic responses via G-protein coupled S1P_1 receptors. In various pathophysiological conditions including psoriasis, oxidative stress exerts deleterious effects on blood vessels, associated with endothelial apoptosis.. We therefore explored whether or not S1P modulates H_2O_2-induced apoptotic responses in cultured bovine aortic endothelial cells (BAEC). BAEC exhibit apoptosis when treated with H_2O_2 (750 μM, for 6 hours), as determined by TUNEL assay (3.5 fold increase of positively stained cells vs. control) and by Cell Death Detection Kit (10.7 fold). H2O2 also promotes cleavage of caspase-3 protein (immunoblot analysis using a subtype-specific antibody, 2.9 fold increase vs. control), a major executor molecule of apoptotic cell death in various cell types, suggesting that oxidative stress promotes apoptosis of BAEC via the caspase-3 pathway. Importantly, when cells have been pre-treated with S1P (1 μM for 30 min) prior to H_2O_2, H_2O_2-induced increases in the numbers TUNEL positive cell as well as the degrees of caspase-3 cleavage are alike attenuated (by 50 and 77 % vs. cells treated by H_2O_2 alone, p < 0.05 respectively). Collectively, these data suggest that a platelet-derived lipid growth factor SIP may protect vascular endothelial cells from oxidative stress-induced apoptotic cell death, possibly representing novel actions of this bioactive lipid on vasculature during wound healing processes.
|
