title: Inhibition of telomerase causes vulnerability to endoplasmic reticulum stress-induced neuronal cell death.
abstract: Endoplasmic reticulum (ER) stress is implicated in several diseases, such as cancer and neurodegenerative diseases. In the present study, we investigated the possible involvement of telomerase in ER stress-induced cell death. ER stress-induced cell death was ameliorated in telomerase reverse transcriptase (TERT) over-expressing MCF7 cells (MCF7-TERT cell). Telomerase specific inhibitor, BIBR1532, reversed the inhibitory effect of TERT on ER stress-induced cell death in MCF7-TERT cells. These findings suggest that BIBR1532 may specifically inhibit telomerase activity, thereby inducing cell death in ER stress-exposed cells. TERT was expressed in the SH-SY5Y neuroblastoma cell line. To analyze the possible involvement of telomerase in ER stress-induced neuronal cell death, we treated SH-SY5Y neuroblastoma cells with BIBR1532 and analyzed ER stress-induced cell death. We found that BIBR1532 significantly enhanced the ER stress-induced neuronal cell death. These findings suggest that inhibition of telomerase activity may enhance vulnerability to neuronal cell death caused by ER stress.
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Electronic address: toruh@hiroshima-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoi
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakatsu
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimamoto
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Electronic address: ozawak@hiroshima-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D062365:Aminobenzoates / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D009281:Naphthalenes / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D062365:Aminobenzoates; C458523:BIBR 1532; D009281:Naphthalenes; D019098:Telomerase
keywords: Endoplasmic reticulum stress; Neurodegenerative disease; Telomerase; Telomerase reverse transcriptase