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Cell Death Dis. 2014 Jul 17;5:e1332. doi: 10.1038/cddis.2014.301.

Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor.

Author information

1
1] Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan [2] Department of Psychiatry, Osaka General Medical center, Sumiyoshi-ku, Osaka, Japan.
2
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
3
Department of Psychiatry, Osaka General Medical center, Sumiyoshi-ku, Osaka, Japan.
4
Gifu Pharmaceutical University, Department of Biofunctional Molecules, Gifu, Japan.
5
Department of Biochemistry, Graduate School of Biomedical & Health Sciences Hiroshima University, Hiroshima, Japan.
6
Team II Endogenous Neuroprotection in Neurodegenerative Diseases INSERM U. 710, EPHE, University of Montpellier cc 105, place Eugene Bataillon, Montpellier cedex 5, France.
7
Department of Psychiatry, Osaka University Health Care Center, Toyonaka, Osaka, Japan.

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.

PMID:
25032855
PMCID:
PMC4123092
DOI:
10.1038/cddis.2014.301
[Indexed for MEDLINE]
Free PMC Article

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