title: Overexpression of bcl-2, bcl-XL or hsp70 in murine cortical astrocytes reduces injury of co-cultured neurons.
abstract: Astrocytes perform many functions that protect neurons during stress, including transmitter uptake, metabolic support, and protection from oxidative stress. We asked whether astrocytes overexpressing either the anti-apoptotic genes bcl-2, or bcl-XL, or the inducible heat shock protein hsp70, could better protect neurons grown with them in co-culture than normal astrocytes or astrocytes expressing beta-galactosidase. Retroviral vectors were used to express these genes in primary astrocyte cultures. After antibiotic selection to eliminate untransformed astrocytes, neurons were plated on top of the astrocytes. Overexpression of any of the three genes in astrocytes reduced neuronal injury induced by combined oxygen-glucose deprivation, or glucose deprivation. Hsp70 overexpression reduced glutamate toxicity. As none of the genes studied is thought to be secreted, the likeliest explanation for the protection observed is improved astrocyte function.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, CA 94305-5123, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
authors.forename: R G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018920:Coculture Techniques; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000506:poisoning; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012016:Reference Values; D051020:bcl-X Protein; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C494812:Bcl2l1 protein, mouse; D018840:HSP70 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D018698:Glutamic Acid; D001616:beta-Galactosidase; D005947:Glucose