title: Oxygen-Glucose Deprivation (OGD) Modulates the Unfolded Protein Response (UPR) and Inflicts Autophagy in a PC12 Hypoxia Cell Line Model.
abstract: Hypoxia is the lack of sufficient oxygenation of tissue, imposing severe stress upon cells. It is a major feature of many pathological conditions such as stroke, traumatic brain injury, cerebral hemorrhage, perinatal asphyxia and can lead to cell death due to energy depletion and increased free radical generation. The present study investigates the effect of hypoxia on the unfolded protein response of the cell (UPR), utilizing a 16-h oxygen-glucose deprivation protocol (OGD) in a PC12 cell line model. Expression of glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94), key players of the UPR, was studied along with the expression of glucose-regulated protein 75 (GRP75), heat shock cognate 70 (HSC70), and glyceraldehyde 3-phosphate dehydrogenase, all with respect to the cell death mechanism(s). Cells subjected to OGD displayed upregulation of GRP78 and GRP94 and concurrent downregulation of GRP75. These findings were accompanied with minimal apoptotic cell death and induction of autophagy. The above observation warrants further investigation to elucidate whether autophagy acts as a pro-survival mechanism that upon severe and prolonged hypoxia acts as a concerted cell response leading to cell death. In our OGD model, hypoxia modulates UPR and induces autophagy.
authors.affiliation: Laboratory of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Theofanis
authors.initials: T
authors.lastname: Vavilis
authors.affiliation: Laboratory of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Nikoleta
authors.initials: N
authors.lastname: Delivanoglou
authors.affiliation: Laboratory of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Aggelidou
authors.affiliation: Laboratory of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Stamoula
authors.affiliation: Laboratory of Physiology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Mellidis
authors.affiliation: Laboratory of Histology, Embryology and Anthropology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Kaidoglou
authors.affiliation: Department of Pathology, General Hospital of Thessaloniki "G. Papanikolaou", Thessaloniki, Greece.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Cheva
authors.affiliation: Laboratory of Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Chryssa
authors.initials: C
authors.lastname: Pourzitaki
authors.affiliation: Unit of Human Reproduction, 1st Department of Obstetrics and Gynaecology, Aristotle University Medical School, Papageorgiou General Hospital, Thessaloniki, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Chatzimeletiou
authors.affiliation: Laboratory of Physiology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Antigone
authors.initials: A
authors.lastname: Lazou
authors.affiliation: Laboratory of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Albani
authors.affiliation: Laboratory of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece. kritis@med.auth.gr.
authors.forename: Aristeidis
authors.initials: A
authors.lastname: Kritis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000502:physiology*; D015687:Cell Hypoxia; D002470:Cell Survival; D000091342:Endoplasmic Reticulum Chaperone BiP; D005947:Glucose / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D005947:Glucose; D010100:Oxygen
keywords: Autophagy; Chaperones; Glucose-regulated proteins; Hypoxia; Oxygen–glucose deprivation; Unfolded protein response