Redox perturbations in cysteamine-stressed astroglia: Implications for inclusion formation and gliosis in the aging brain

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

“…This latter observation is consistent with previous reports that intracellular transport of low molecular weight inorganic iron may be far more efficient than that of transferrin-bound iron in certain tissues (Richardson and Ponka, 1997) and is commensurate with reports that transferrin binding sites are enigmatically deficient in PD-affected neural tissues exhibiting iron overload (Mash et al, 1991;Gelman, 1995;Faucheux et al, 1997). Within several hours of CSH exposure and long before mitochondrial iron sequestration becomes manifest, cultured astroglia exhibit robust increases in heme oxygenase-1 (HO-1) mRNA and protein levels and enzymatic activity (Mydlarski et al, 1993;Chopra et al, 1995;Manganaro et al, 1995). The HO-1 gene has a heat shock element in its promoter region and is strongly up-regulated by oxidative stress, metal ions, sulfhydryl compounds, and hyperthermia.…”

“…A s in the case of CSH (Mydlarski e t al., 1993;Chopra eta]., 1995; Manganaro et al, 1995), physiologically and pharmacologically relevant concentrations of DA (1 -100 pM) rapidly (within 3-6 h) augmented HO-1 mRNA levels in primary cultures of neonatal rat astroglia (Fig. 1A and B).…”

Resistance of Mitochondrial DNA-depleted Cells against Cell Death

“…10A). We next studied the role of HO-1 whose expression was increased more than 4-fold in our DNA chip analysis and which has been reported to induce MnSOD in response to oxidative stress (34,35). A strong induction of HO-1 in SK-Hep1 0 cells was confirmed by RT-PCR analysis (Fig.…”

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

“…Manganaro et al (1995) (Issels et al, 1988), OvCa cells (Isse1s and Nagele, 1990) and mouse fibroblasts (Djurhuus et al, 1990) following CSH exposure. CSH induces the synthesis of GSH by 1) forming mixed (lisulfides with extraceUu1ar cystine thereby generating the GSH precursor, cysteine and 2) promoting the transport of cysteine into ceUs where it can be utilized for de IIOVO GSH biosynthesis (Isse1s et al, 1988).…”

“…CSI-I, in the presence of transition metals, undergoes redox cycling with the generation of pro-oxidant species inciuding thiyl radicals, 02', H202 and HO· (Munday, 1989). Recently, Manganaro et al (1995) . These seemingly contradictory effects of CSH on lipid peroxidation may be due to the fact that CSH and other aminothiols may behave as either pro-or anti-oxidants depending upon their redox microenviroment (Munday, 1989;Weiss and Kumar , 1994).…”