The mechanisms of 6-hydroxydopamine-induced astrocyte death.
Treatment with 6-hydroxydopamine significantly reduced the viability of cultured rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. 6-Hydroxydopamine-treated astrocytes exhibited altered nuclear morphology, DNA fragmentation, and reduced intracellular esterase activity, which indicated apoptotic cell death. Astrocytes were protected by neutralization of 6-hydroxydopamine autooxidation products H(2)O(2), O(2)(*-), and (*)OH, but not by cell-derived or chemically generated anti-apoptotic free radical nitric oxide. Finally, 6-hydroxydopamine activated extracellular signal-regulated kinase in astrocytes and selective inhibitor of extracellular signal-regulated kinase activation partially prevented astrocyte death. Taken together, these data indicate that 6-hydroxydopamine-triggered oxidative stress induces extracellular signal-regulated kinase-dependent apoptotic death of astrocytes.
Raicević
Nevena
N
Institute for Biological Research Sinisa Stanković, Belgrade, Serbia and Montenegro. nevenar@ibiss.bg.ac.yu
Mladenović
Aleksandra
A
Perović
Milka
M
Miljković
Djordje
D
Trajković
Vladimir
V
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D018663:Adrenergic Agents; D005609:Free Radicals; D009569:Nitric Oxide; D016627:Oxidopamine; D048049:Extracellular Signal-Regulated MAP Kinases; D004950:Esterases