| Project/Area Number |
17K08245
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Physical pharmacy
|
|---|
| Research Institution | International University of Health and Welfare |
|---|
Principal Investigator |
MIURA Takashi 国際医療福祉大学, 薬学部, 教授 (30222318)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | 酸化ストレス / オピオイドペプチド / セロトニン / 銅 / 神経変性疾患 / 分光法 / 脳神経疾患 |
|---|
| Outline of Final Research Achievements |
Copper may lead to generation of toxic reactive oxygen species (ROS) due to its redox activity. Therefore, cellular uptake, storage and export of copper have to be tightly regulated in order to prevent copper-induced oxidative stress. Brain is considered to be vulnerable to oxidative damage because of its high oxygen consumption and lipid content. However, mechanism for anti-oxidative defense system in brain is still not well understood.
In the research project, we found that endomorphin 1 (EM1), endogenous opioid peptide, is capable of binding copper ion, either Cu(II) or Cu(I), in the SDS micelle-bound state. EM1 may play a part in protection of cellular lipids from ROS-induced oxidation.
We also examined anti-oxidative roles of neurotransmitter serotonin (5-HT), and found that 5-HT exhibits a high Cu(II) reducing activity in the presence of thioethers, such as the Met-rich region of copper transporter Ctr1. Reduction of extracellular Cu(II) may be another physiological role of 5-HT.
|
| Academic Significance and Societal Importance of the Research Achievements |
銅は、細胞障害を引き起こす酸化ストレスの直接の発生原因となるため、銅の酸化還元制御のメカニズムを解明することは大きい意義を持つ。本研究で得られた知見は、オピオイドペプチドや神経伝達物質が脳における銅恒常性に関わることを強く示唆する。このため、本研究の成果は、脳における銅酸化還元制御のメカニズムの解明に繋がることが強く期待でき、酸化ストレスに起因する多くの疾患、例えばアルツハイマー病などの発症原因を解明する上での重要な基礎となる。従来と異なる発想に基づく治療薬開発への道が開かれるなど、本研究は発展性と波及効果の点においても大きい可能性を持つ。
|
