title: Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor.
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.
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Omi
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanimukai
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Kanayama
authors.affiliation: Department of Psychiatry, Osaka General Medical center, Sumiyoshi-ku, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakagami
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tagami
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okochi
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Morihara
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yanagida
authors.affiliation: Gifu Pharmaceutical University, Department of Biofunctional Molecules, Gifu, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kitasyoji
authors.affiliation: Gifu Pharmaceutical University, Department of Biofunctional Molecules, Gifu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Biochemistry, Graduate School of Biomedical & Health Sciences Hiroshima University, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imaizumi
authors.affiliation: Team II Endogenous Neuroprotection in Neurodegenerative Diseases INSERM U. 710, EPHE, University of Montpellier cc 105, place Eugene Bataillon, Montpellier cedex 5, France.
authors.forename: T
authors.initials: T
authors.lastname: Maurice
authors.affiliation: Team II Endogenous Neuroprotection in Neurodegenerative Diseases INSERM U. 710, EPHE, University of Montpellier cc 105, place Eugene Bataillon, Montpellier cedex 5, France.
authors.forename: N
authors.initials: N
authors.lastname: Chevallier
authors.affiliation: Team II Endogenous Neuroprotection in Neurodegenerative Diseases INSERM U. 710, EPHE, University of Montpellier cc 105, place Eugene Bataillon, Montpellier cedex 5, France.
authors.forename: S
authors.initials: S
authors.lastname: Marchal
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Psychiatry, Osaka University Health Care Center, Toyonaka, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kudo
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D016666:Fluvoxamine / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017480:Receptors, sigma / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation / Q000187:drug effects*; D000097605:Sigma-1 Receptor
chemical_list: D051701:Activating Transcription Factor 4; D016666:Fluvoxamine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor