Back to Search
Start Over
Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor.
- Source :
-
Cell death & disease [Cell Death Dis] 2014 Jul 17; Vol. 5, pp. e1332. Date of Electronic Publication: 2014 Jul 17. - Publication Year :
- 2014
-
Abstract
- We recently demonstrated that endoplasmic reticulum (ER) stress induces sigma-1 receptor (Sig-1R) expression through the PERK pathway, which is one of the cell's responses to ER stress. In addition, it has been demonstrated that induction of Sig-1R can repress cell death signaling. Fluvoxamine (Flv) is a selective serotonin reuptake inhibitor (SSRI) with a high affinity for Sig-1R. In the present study, we show that treatment of neuroblastoma cells with Flv induces Sig-1R expression by increasing ATF4 translation directly, through its own activation, without involvement of the PERK pathway. The Flv-mediated induction of Sig-1R prevents neuronal cell death resulting from ER stress. Moreover, Flv-induced ER stress resistance reduces the infarct area in mice after focal cerebral ischemia. Thus, Flv, which is used frequently in clinical practice, can alleviate ER stress. This suggests that Flv could be a feasible therapy for cerebral diseases caused by ER stress.
- Subjects :
- Activating Transcription Factor 4 genetics
Activating Transcription Factor 4 metabolism
Animals
Apoptosis drug effects
HEK293 Cells
Humans
Male
Mice
Mice, Knockout
Neurons cytology
Neurons drug effects
Neurons metabolism
Receptors, sigma metabolism
Signal Transduction
Sigma-1 Receptor
Endoplasmic Reticulum Stress drug effects
Fluvoxamine pharmacology
Receptors, sigma genetics
Up-Regulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 25032855
- Full Text :
- https://doi.org/10.1038/cddis.2014.301