title: Effects of Estrogen and Phytoestrogen Treatment on an In Vitro Model of Recurrent Stroke on HT22 Neuronal Cell Line.
abstract: An increase of stroke incidence occurs in women with the decline of estrogen levels following menopause. This ischemic damage may recur, especially soon after the first insult has occurred. We evaluated the effects of estrogen and phytoestrogen treatment on an in vitro recurrent stroke model using the HT22 neuronal cell line. HT22 cells were treated with 17β-estradiol or genistein 1 h after the beginning of the first of two oxygen and glucose deprivation/reoxygenation (OGD/R) cycles. During the second OGD, there was a deterioration of some components of the electron transport chain, such as cytochrome c oxidase subunit 1 with a subsequent increase of reactive oxygen species (ROS) production. Accordingly, there was also an increase of apoptotic phenomena demonstrated by poly(ADP-ribose) polymerase 1 cleavage, Caspase-3 activity, and Annexin V levels. The recurrent ischemic injury also raised the hypoxia-inducible factor 1α and glucose transporter 1 levels, as well as the ratio between the lipidated and cytosolic forms of microtubule-associated protein 1A/1B-light chain 3 (LC3-II/LC3-I). We found a positive effect of estradiol and genistein treatment by partially preserving the impaired cell viability after the recurrent ischemic injury; however, this positive effect does not seem to be mediated neither by blocking apoptosis processes nor by decreasing ROS production. This work contribute to the better understanding of the molecular mechanisms triggered by recurrent ischemic damage in neuronal cells and, therefore, could help with the development of an effective treatment to minimize the consequences of this pathology.
authors.affiliation: Department of Functional Biology. Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006, Oviedo, Spain.|Department of Clinical Neuroscience and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 9A, Box 440, 413 90, Gothenburg, Sweden.
authors.forename: Javier
authors.initials: J
authors.lastname: Morán
authors.affiliation: Unit of Transplants, Cell Therapy and Regenerative Medicine, Central University Hospital of Asturias, Av. Roma s/n, 33011, Oviedo, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Perez-Basterrechea
authors.affiliation: Department of Functional Biology. Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006, Oviedo, Spain.|Prostate Cancer Institute, National University of Ireland, Galway. Co, Galway, Ireland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garrido
authors.affiliation: Department of Functional Biology. Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006, Oviedo, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Díaz
authors.affiliation: Department of Functional Biology. Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Unit of Transplants, Cell Therapy and Regenerative Medicine, Central University Hospital of Asturias, Av. Roma s/n, 33011, Oviedo, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Otero
authors.affiliation: Service of Hematology, Central University Hospital of Asturias, Av/Roma s/n, 33011, Oviedo, Spain.|Department of Laboratory Medicine, Central University Hospital of Asturias, Av/Roma s/n, 33011, Oviedo, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Colado
authors.affiliation: Department of Functional Biology. Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006, Oviedo, Spain. tinog@uniovi.es.
authors.forename: Celestino
authors.initials: C
authors.lastname: González
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000172:deficiency; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D004967:Estrogens; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008869:Microtubule-Associated Proteins; D048789:Phytoestrogens; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; D003576:Electron Transport Complex IV; D011065:Poly(ADP-ribose) Polymerases; D005947:Glucose; D010100:Oxygen
keywords: 17β-estradiol; Apoptosis; Genistein; HT22 cells; Oxidative metabolism; Recurrent stroke