| RRC ID |
59879
|
| 著者 |
Asano M, Motoike S, Yokota C, Usuki N, Yamamoto H, Urabe T, Katarao K, Hide I, Tanaka S, Kawamoto M, Irifune M, Sakai N.
|
| タイトル |
SKF-10047, a prototype Sigma-1 receptor agonist, augmented the membrane trafficking and uptake activity of the serotonin transporter and its C-terminus-deleted mutant via a Sigma-1 receptor-independent mechanism.
|
| ジャーナル |
J Pharmacol Sci
|
| Abstract |
The serotonin transporter (SERT) is functionally regulated via membrane trafficking. Our previous studies have demonstrated that the SERT C-terminal deletion mutant (SERTΔCT) showed a robust decrease in its membrane trafficking and was retained in the endoplasmic reticulum (ER), suggesting that SERTΔCT is an unfolded protein that may cause ER stress. The Sigma-1 receptor (SigR1) has been reported to attenuate ER stress via its chaperone activity. In this study, we investigated the effects of SKF-10047, a prototype SigR1 agonist, on the membrane trafficking and uptake activity of SERT and SERTΔCT expressed in COS-7 cells. Twenty-four hours of SKF-10047 treatment (>200 μM) accelerated SERT membrane trafficking and robustly upregulated SERTΔCT activity. Interestingly, these effects of SKF-10047 on SERT functions were also found in cells in which SigR1 expression was knocked down by shRNA, suggesting that SKF-10047 exerted these effects on SERT via a mechanism independent of SigR1. A cDNA array study identified several candidate genes involved in the mechanism of action of SKF-10047. Among them, Syntaxin3, a member of the SNARE complex, was significantly upregulated by 48 h of SKF-10047 treatment. These results suggest that SKF-10047 is a candidate for ER stress relief.
|
| 巻・号 |
139(1)
|
| ページ |
29-36
|
| 公開日 |
2019-1-1
|
| DOI |
10.1016/j.jphs.2018.11.005
|
| PII |
S1347-8613(18)30206-8
|
| PMID |
30522963
|
| MeSH |
Animals
COS Cells
Cell Membrane / drug effects*
Cell Membrane / metabolism
Chlorocebus aethiops
Endoplasmic Reticulum Stress
Gene Knockdown Techniques
Mutation
Phenazocine / analogs & derivatives*
Phenazocine / pharmacology
Protein Transport
Receptors, sigma / agonists*
Receptors, sigma / genetics
Serotonin Plasma Membrane Transport Proteins / physiology*
|
| IF |
2.835
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
