| Project/Area Number |
17K01359
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Biomedical engineering/Biomaterial science and engineering
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
Kaihara Keiko 岡山大学, 医学部, 技術専門職員 (60638641)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
入部 玄太郎 岡山大学, 医歯薬学総合研究科, 准教授 (90284885)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | NADPH oxidase 4 / 活性酸素（ROS) / メカノトランスダクション / 単離心筋細胞 / 圧負荷 / 心不全 / NADPH oxidase 4（NOX4) / 活性酸素（ROS） / NOX4 / 活性酸素( ROS ) / 生理学 / 循環器・高血圧 / 生理活性 |
|---|
| Outline of Final Research Achievements |
Reactive oxygen species (ROS) synthesized by NADPH oxidase (NOX) in vivo is a very important physiologically active substance. Although, myocardial stretch-induced ROS production via NOX2 modulates Ca2+ handling and cellular contractility, behavior of NOX4 is unknown. In the present study, we investigated the physiological and pathophysiological role of NOX4 in cardiac mechano-transduction.
Ventricular cells isolated were subjected to 5-10% axial stretch with the cardiomyocyte stretch system, were measured ROS production, Ca2+ spark rate, mitochondrial membrane potential and cellular contractility. Cellular contractility and ROS production were significantly suppressed in NOX2 KO and NOX4 KO, but Ca2+ spark rate was suppressed only in NOX2 KO. The results suggest that role of NOX4 during stretch is different from that of NOX2. On the other hand, from the results of TAC model mice, there was an effect of NOX4 on overload, but details could not be clarified.
|
| Academic Significance and Societal Importance of the Research Achievements |
ROSは、様々な疾患や老化などに影響する負のイメージが強いが、実は生体防御機構である免疫や細胞の分化などに関与する生命活動に非常に重要な生理活性物質である。心臓においては、前負荷増大時に収縮力が増加するというフランク・スターリングの法則に、ROSが関与しており、心臓生理を理解する上ではROSは重要な生理活性物質となる。
本研究結果より明らかとなったNOX4由来のROSのフランク・スターリングの法則への関与は、今後の心臓生理を理解する上で非常に重要である。また、慢性的な圧負荷に関するNOX4の関与解明は、心不全治療への応用となりうる可能性があることから今後のさらなる研究に期待できる。
|
