Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study.
In rodents, chronic estrogenization has been shown to induce degeneration of dendrites and myelin figures in the hypothalamic arcuate nucleus adjacent to peroxidase-positive astrocyte processes. Because in this brain region estradiol is metabolized to 2-hydroxyestradiol (catecholestrogen), we hypothesized that the latter may be oxidized by the astrocytic peroxidase activity to cytotoxic ortho-semiquinones as occurs in peripheral tissues. Cysteamine induces nonenzymatic peroxidase activity in cultured astroglia identical to that observed in vivo. Using electron spin resonance, we demonstrate robust peroxidase-catalyzed oxidation of 2-hydroxyestradiol and dopamine by cysteamine-pretreated astrocyte cultures relative to untreated controls. These results implicate the peroxidase-positive astrocytes in the pathogenesis of estradiol-related hypothalamic damage, parkinsonism, and other free-radical-related neurologic disorders.
Schipper
H M
HM
Department of Neurology, McGill University, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Kotake
Y
Y
Janzen
E G
EG
D015100:3,3'-Diaminobenzidine; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D016227:Benzoquinones / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D002478:Cells, Cultured; D003543:Cysteamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006651:Histocytochemistry; D009249:NADP / Q000494:pharmacology; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling
D016227:Benzoquinones; D005904:Glial Fibrillary Acidic Protein; D015100:3,3'-Diaminobenzidine; C025232:semiquinone radicals; D004958:Estradiol; D009249:NADP; D003543:Cysteamine; C001390:2-hydroxyestradiol; D009195:Peroxidase; D004298:Dopamine