Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study

Abstract

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.

Mitochondrial Iron Sequestration in Dopamine‐Challenged Astroglia: Role of Heme Oxygenase‐1 and the Permeability Transition Pore

“…The glial mitochondrial iron is maintained in the highly reactive ferrous state by reducing equivalents of the electron transport chain and behaves as a nonenzymatic peroxidase activity capable of oxidizing DA and other catechols to neurotoxic ortho-semiquinone radicals (Schipper et al, 1991). The latter promote further oxidative stress, thereby amplifying damage to vulnerable glial and neuronal constituents within the PD nigra (Schipper, 1996;Frankel and Schipper, 1997).…”

Differential effects of cysteamine on heat shock protein induction and cytoplasmic granulation in astrocytes and glioma cells

“…Indeed, the numbers of Gomori-granules and lipofuscin both increase progressively with age. However, the atypical autofluorescence pattern and the absence of neutra1 lipid (negative Sudan Black and Sudan III reactions) and visible pigment under light microscopy exclude lipofuscin as a component of these astrocytic granules (Schipper, 1991).…”

“…Astrocytes are the most numerous and diversified class of neuroglia in the fetal and mature CNS (Schipper, 1991). Astrocytes can be identified by their stellate perlkarya and numerous processes which extend into the surrounding neuropil (Carpenter, 1983).…”

“…Gomori-positive astrocytes are a unique subpopulation of granule-Iaden neuroglia found in the hippocampus, striatum, and periventricular brain regions of all vertebrate species examined to date, including humans (Schipper, 1991). These astrocytes contain~.…”

“…Chrome alum hematoxylin stllins basically the same structures as a1dehyde fuchsin with the exception of neuronal perikarya (Creswell et al, 1964;Noda, 1959;Wislocki and Leduc, 1954). Based on their tinctorial characteristics, the Gomori-positive inclusions were believcd to he li form of lipofuscin or a phagocytosed neurosecretion (Lofgreen, 1961;Noda, 1959, Schipper, 1991. Indeed, the numbers of Gomori-granules and lipofuscin both increase progressively with age.…”