Elucidation of mechanisms that cigarette smoking causes vascular wall injury through oxidative stress
| Project/Area Number |
16590100
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Environmental pharmacy
|
|---|
| Research Institution | Mukogawa Women's University |
|---|
Principal Investigator |
KUNITOMO Masaru Mukogawa Women's University, School of Pharmacy and Pharmaceutical Sciences, Professor, 薬学部, 教授 (40125133)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Yu Mukogawa Women's University, School of Pharmacy and Pharmaceutical Sciences, Assistant, 薬学部, 助手 (90183681)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | Cigarette smoking / Atherosclerosis / Oxidative stress / Peroxynitrite / Peroxynitrite-like reactants / Oxidized LDL / 8-OHdG / 3-Nitrotyrosine / Peroxynitrite / 3-Nitrotyrosine / アポE欠損マウス / たばこ煙水抽出液 / 3-Nitorotyrosine / 肺胞壁 / ラット / 肺胞膜 / マトリゲル |
|---|
| Research Abstract |
Overwhelming evidence shows that cigarette smoking is an important risk factor for atherosclerotic vascular diseases. However, the underlying factors of this deleterious effect are not fully understood. We have demonstrated that aqueous extracts of cigarette smoke (CSE) contain stable peroxynitrite-like reactants that cause oxidation and nitration of low-density lipoprotein (LDL) in vitro and in vivo, and suggested that such oxidants are associated with systemically increased oxidative and nitrative stress in cigarette smokers. We have also found that the oxidants in CSE easily pass through the basement membrane matrix (Matrigel) and the pulmonary alveolar wall of isolated rat lungs. CSE did not activate the rat alveolar macrophages in vitro. When rats were acutely exposed to the gas-phase cigarette smoke, which removed tar and nicotine, circulating oxidative LDL (a marker of oxidative stress), 8-hydroxy-2'-deoxyguanine (a marker of oxidative DNA damage) and 3-nitrotyrosine (a marker of peroxynitrite) levels rapidly increased. CSE induced apoptosis in the endothelial cells in vitro. In addition, the apolipoprotein E-deficient mice exposed to cigarette smoke for 16 weeks, 15 min a day, displayed marked increases in serum TBARS, oxidative LDL, 3-nitrotyrosine levels and marked increases in cholesteryl ester levels together with 3-nitrotyrosine levels in the aorta. These changes in the serum and aorta were effectively prevented by administration of vitamin E. Our results suggest that peroxynitrite-like reactants in cigarette smoke can penetrate the pulmonary alveolar wall and cause the oxidized LDL formation and vascular endothelial cell injury, consequently leading to the development of atherosclerosis. At present, we are separating and identifying peroxynitrite-like reactants in CSE by using HPLC and LC/MS analysis.
|
Report
(4 results)
Research Products
(27 results)
