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The Mechanisms of 6‐Hydroxydopamine‐Induced Astrocyte Death
Author(s) -
RAIČEVIĆ NEVENA,
MLADENOVIĆ ALEKSANDRA,
PEROVIĆ MILKA,
MILJKOVIĆ DJORDJE,
TRAJKOVIĆ VLADIMIR
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1342.049
Subject(s) - hydroxydopamine , astrocyte , extracellular , apoptosis , programmed cell death , microbiology and biotechnology , dna fragmentation , kinase , chemistry , intracellular , fragmentation (computing) , biology , biochemistry , neuroscience , central nervous system , ecology , dopaminergic , dopamine
A bstract : 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.