2017 Fiscal Year Final Research Report
Underlying mechanism of cytoprotective effects and regulation of mu-opioid receptor induced by sigma-1-receptor chaperone
| Project/Area Number |
15K07977
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pharmacology in pharmacy
|
|---|
| Research Institution | Hoshi University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Keywords | Sigma-1 receptor / Morphine / Bcl-2 / withdrawal symptom |
|---|
| Outline of Final Research Achievements |
The present study was designed to delineate the possible involvement of Bcl-2 in the cytoprotective effects of Sig-1R against mitochondria originated apoptosis in cells. We expected that Sig-1R may exert cytoprotective effects against mitochondria oriented stress through regulation of Bcl-2, however our findings indicate that Sig-1R as well as Bcl-2 regulates mitochondria-originated apoptosis through different ways; Sig-1R and Bcl-2 at mitochondria could regulate the caspase pathway and phosphorylation of GSK-3β to protect the cells, respectively.
Sig-1R as an ER chaperone is upregulated to protect cells against long-term stimulation of MOR1C, and sabotage its assigned functions by translocation induced by unexpected stimuli. Thus, Sig-1R is an important molecule in the maintaining the homeostasis and the expression of withdrawal signs in the morphine-adapted state. Our findings indicate that Sig-1R antagonists could be a candidate for the treatment of opioid withdrawal symptoms.
|
| Free Research Field |
行動薬理
|
