Dual effect of nitric oxide on cell death : Induction and protection of apoptosis
| Project/Area Number |
13672314
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Setsunan University |
|---|
Principal Investigator |
MAEDA Sadaaki Setsunan Univ., Faculty of Pharmaceut. Sci., Professor, 薬学部, 教授 (00135732)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAMURO Akiko Setsunan Univ., Faculty of Pharmaceut. Sci., Research Associate, 薬学部, 助手 (20340862)
YOSHIOKA Yasuhiro Setsunan Univ., Faculty of Pharmaceut. Sci., Research Associate, 薬学部, 助手 (40330360)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
|
|---|
| Keywords | nitric oxide / apoptosis / cyclic GMP / cytochrome c / RAW 264 cells / protein kinase G / Bax / 一酸化炭素 / Cyclic GMP / Protein kinase G |
|---|
| Research Abstract |
We investigated the protective effect of nitric oxide (NO) at a low concentration on cell death induced by NO and its mechanism in human neuroblastoma SH-SY5Y cells and mouse macrophage cell line, RAW264.
Sodium nitroprusside (SNP), an NO donor, induced cell death in SH-SY5Y cells. Pretreatment with NOC12, an NO donor, at a low concentration partially prevented the cell death induced by SNP. Pretreatment with cyclic GMP analogues, dibutyryl-cGMP, prevented SNP-induced cell death. NOC12 at a low concentration, which has no effect on the cell viability, induced cell death in the presence of a guanylate cyclase inhibitor, LY83583. The cell death was partially protected by dibutyryl-cGMP. These results suggest that cGMP has a protective effect on NO-induced cell death in SH-SY5Y cells.
Pretreatment with 100 μM SNP for 24h prevented the cell death and cytochrome c release induced by 4 mM SNP in RAW264 cells. The effect of SNP pretreatment was reduced by LY83583 (guanylyl cyclase inhibitors). Pretreatment with DBcGMP prevented cell death induced by NOC18, GSNO or SNP, in a concentration- dependent manner. Pretreatment with DBcGMP prevented cytochrome c release induced by NO donors. The protective effect of SNP or DBcGMP was significantly attenuated by KT5823 (a protein kinase G inhibitor). These results indicate that NO at a low concentration protects RAW264 cells from the cytotoxicity of NO through cGMP production and activation of PKG.
|
Report
(3 results)
Research Products
(3 results)
