title: Naloxone induces endoplasmic reticulum stress in PC12 cells.
abstract: Naloxone is an opioid inverse agonist used in the treatment of opiate overdose, with well known pharmacology. In the present study, we determined the effects of naloxone on the unfolded protein response (UPR) in PC12 cells. Data from a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that naloxone may accelerate PC12 cell apoptosis in a dose-dependent manner. We also demonstrated that naloxone upregulated gene expression of endoplasmic reticulum (ER) chaperones, including binding immunoglobulin protein (Bip), calnexin, ER protein 29 (ERp29) and protein disulfide isomerase (PDI), and ER stress sensors, including activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1) and protein kinase-like ER kinase (PERK). In addition, naloxone also induced typical ER stress phenomena, including ART6 proteolytic cleavage, eIF2α phosphorylation and XBP1 mRNA splicing. Furthermore, naloxone upregulated gene expression of ER chaperones and ER stress sensors in in vivo experiments. To the best of our knowledge, these results are the first to indicate that naloxone induces ER stress in vitro and in vivo.
authors.affiliation: Inje University Busan-Paik Hospital, Busan 614-735, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Seo
authors.affiliation: Department of Nursing, JoongBu University, Geumsan 312‑702, Republic of Korea.
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Korea Research Institute of Bioscience & Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Kweon
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Emergency Medicine, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: O-Yu
authors.initials: OY
authors.lastname: Kwon
authors.affiliation: Department of Dental Hygiene, Konyang University, Daejeon 301-832, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kang
authors.affiliation: Department of Biomedical Laboratory Science, College of Health and Welfare, Kyungwoon University, Gumi 730-739, Republic of Korea.
authors.forename: Kisang
authors.initials: K
authors.lastname: Kwon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009270:Naloxone / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D018832:Molecular Chaperones; D009270:Naloxone