title: Oxidized proteins in astrocytes generated in a hyperbaric atmosphere induce neuronal apoptosis.
abstract: In the present study, we investigated the influence of the oxidative damage to astrocytes on neuronal cell survival using cultures of rat cerebral astrocytes and neurons. The exposure of astrocytes to hyperbaric oxygen induced a time-dependent apoptotic cell death, as observed by DNA ladder assessment. When astrocytes damaged by oxidative stress were cocultured with normal neurons from the cerebrum of a newborn rat, neuronal cell death was markedly induced, although normal astrocytes not subjected to hyperoxia cocultured with normal neurons showed no neuronal cell apoptosis. It was found that either the supernatant from the homogenate of astrocytes cultured in hyperbaric oxygen atmosphere or a protein mixture extracted from the supernatant induced neuronal cell death. The level of protein carbonyls, an index of protein oxidation analysis, in cultured astrocytes increased significantly with oxidative stress, and vitamin E inhibited the increase in the level of such oxidized proteins in astrocytes. Furthermore, a two-dimensional (2D) electrophoresis of a protein mixture extracted from the supernatant showed several changes in proteins. These results imply that reactive oxygen species (ROS) induced by oxidative stress attack astrocytes to induce oxidatively denatured proteins in the cells that act as a neurotoxic factor, and that vitamin E protects neurons by inhibiting astrocyte apoptosis caused by oxidative stress.
authors.affiliation: Division of Biological Chemistry, Shibaura Institute of Technology, 3-7-5 Toyosu, Kohtoh-ku, Tokyo 135-8548, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Mori
authors.forename: Masayuki
authors.initials: M
authors.lastname: Oikawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tamagami
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kumaki
authors.forename: Reiko
authors.initials: R
authors.lastname: Nakaune
authors.forename: Jun
authors.initials: J
authors.lastname: Amano
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Akinaga
authors.forename: Koji
authors.initials: K
authors.lastname: Fukui
authors.forename: Kouichi
authors.initials: K
authors.lastname: Abe
authors.forename: Shiro
authors.initials: S
authors.lastname: Urano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D006931:Hyperbaric Oxygenation; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation; D051381:Rats; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D014810:Vitamin E