title: Glutathione release and catabolism during energy substrate restriction in astrocytes.
abstract: This study examined the effect of simulated ischemia (deprivation of both oxygen and substrate) on astrocyte reduced-glutathione (GSH). We have demonstrated that under normoxic conditions there is no GSH efflux from living astrocytes; this suggests that the high levels of GSH in astrocytes in vivo are not available for neighbouring neural cells. Under simulated ischemia there is release of GSH from astrocytes only when astrocytes die. Furthermore, when astrocytic energy stores are depleted GSH is catabolized, such that after 12 h of simulated ischemia approximately 20% of GSH is catabolized. This GSH catabolism can be increased at an earlier time by causing increased ATP utilization through activating the sodium pump either by introducing glutamate into the culture medium or by raising medium potassium. Since GSH is catabolized into glycine, glutamate and cysteine, the latter two amino acids being neurotoxic, our findings indicate that the high levels of GSH in astrocytes may be used by these cells to survive ischemic insults, but the catabolism of GSH may result in increased neuronal damage.
authors.affiliation: Saskatchewan Stroke Research Centre, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: B H
authors.initials: BH
authors.lastname: Juurlink
authors.forename: E
authors.initials: E
authors.lastname: Schültke
authors.forename: L
authors.initials: L
authors.lastname: Hertz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D002478:Cells, Cultured; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D013997:Time Factors
chemical_list: D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione