Underlying mechanism of cytoprotective effects and regulation of mu-opioid receptor induced by sigma-1-receptor chaperone
| Project/Area Number |
15K07977
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | Sigma-1 receptor / Morphine / Bcl-2 / withdrawal symptom / GSK-3β / アポトーシス / Sigma-1受容体 / Caspase / シグマ１受容体シャペロン / 神経障害性疼痛 / Paclitaxel |
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| 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.
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Report
(4 results)
Research Products
(4 results)
