title: 17beta-estradiol attenuates hyperoxia-induced apoptosis in mouse C8-D1A cell line.
abstract: In premature infants, oxygen free radicals generated following neonatal resuscitation are associated with subsequent diseases such as retinopathy of prematurity and bronchopulmonary dysplasia. Recent studies in brain tissue samples have shown that nonphysiologic oxygen levels play a key role in induction of apoptosis in the developing brain. Estrogen is a well-established agent in neuroprotection and, therefore, is thought to be neuroprotective even in the premature brain. Astrocytes appear to have a critical role in protection and survival of neurons in the brain. As one of the glial cell types, they have a great potential for possible involvement in the mediation of estrogen neuroprotective effects. The aim of our study was to analyze whether astrocytes in cell cultures are damaged by hyperoxia and whether 17beta-estradiol (E2) can protect them against apoptosis. Additionally, we investigated the mechanism of the protection by E2, hypothesizing that it is mediated through extracellular signal-regulated kinase (ERK1/2). Cells underwent eightfold more apoptosis when cultivated in hyperoxia compared with normoxia. Addition of E2 reduced apoptosis in hyperoxia by more than 50%. Levels of ERK1/2 and phosphorylated ERK1/2 were increased after hyperoxia compared with normoxia. Preincubation with E2 prior to exposure to hyperoxia resulted in decreased levels of ERK1/2 and pERK1/2. Hyperoxia induces apoptosis in C8-D1A cells, and E2 seems to be a protecting factor for astrocytes in hyperoxia. This effect is not mediated through up-regulation of pERK1/2.
authors.affiliation: Department of Neonatology, Charité, Campus Virchow Klinikum, Berlin, Germany. stephanie.huppmann@charite.de
authors.forename: Stephanie
authors.initials: S
authors.lastname: Huppmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Römer
authors.forename: Rodica
authors.initials: R
authors.lastname: Altmann
authors.forename: Michael
authors.initials: M
authors.lastname: Obladen
authors.forename: Monika
authors.initials: M
authors.lastname: Berns
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D015153:Blotting, Western; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D004967:Estrogens / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects; D018496:Hyperoxia / Q000188:drug therapy* / Q000503:physiopathology*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D018696:Neuroprotective Agents; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases