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

Chopra, Vikramjit; Chalifour, Lorraine E.; Schipper, Hyman M.

doi:10.1016/0169-328x(95)00049-x

Cited by 37 publications

(30 citation statements)

References 109 publications

(131 reference statements)

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“…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.…”

supporting

confidence: 78%

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

Schipper

Bernier

Mehindate

et al. 1999

Journal of Neurochemistry

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Abstract:Little is currently known concerning the mechanisms responsible for the excessive deposition of redox-active iron in the substantia nigra of subjects with Parkinson's disease (PD). In the present study, we demonstrate that dopamine promotes the selective sequestration of non-transferrin-derived iron by the mitochondrial compartment of cultured rat astroglia and that the mechanism underlying this novel dopamine effect is oxidative in nature. We also provide evidence that up-regulation of the stress protein heme oxygenase-1 (HO-1) is both necessary and sufficient for mitochondrial iron trapping in dopamine-challenged astroglia. Finally, we show that opening of the mitochondrial transition pore (MTP) mediates the influx of non-transferrin-derived iron into mitochondria of dopamine-stimulated and HO-1 -transfected astroglia. Our findings provide an explanation for the pathological iron sequestration, mitochondrial insufficiency, and amplification of oxidative injury reported in the brains of PD subjects. Pharmacological blockade of transition metal trapping by "stressed" astroglial mitochondria (e.g., using HO-1 inhibitors or modulators of the MTP) may afford effective neuroprotection in patients with PD and other neurological afflictions.

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supporting

confidence: 78%

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

Schipper

Bernier

Mehindate

et al. 1999

Journal of Neurochemistry

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“…Cysteamine treatment resulted in increases in HSP 27, HSP 90, and HO-1 at both the protein and mRNA level. In addition, C6 glioma cells, unlike primary astrocytes, constitutively express HSP 27, HSP 90, and HO-1 at low levels (Chopra et al, 1995).…”

Section: O Cancer and Heme Oxygenase-1mentioning

confidence: 99%

Pharmacological and Clinical Aspects of Heme Oxygenase

Abraham

Kappas²

2008

Pharmacol Rev

1,012

1,007

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“…However, the mechanism by which it affects the pathogenesis of HE remains unknown. In normal conditions in the central nervous system, the level of HO-1 expression is low (20). Several studies have demonstrated that HO-1 mRNA expression levels are elevated in the frontal cortex of HE rats, which exerts a number of important effects on the coma stage of encephalopathy induced by liver injury (14,21,22).…”

Section: Discussionmentioning

confidence: 99%

Role of the heme oxygenase/carbon monoxide pathway in the pathogenesis and prevention of hepatic encephalopathy

Wang

Yin

Duan

et al. 2013

Molecular Medicine Reports

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Abstract. Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis and its pathogenesis has yet to be fully elucidated. Previous studies have demonstrated that heme oxygenase-1 (HO-1) is important in the induction of liver cirrhosis. The present study aimed to investigate the role of HO-1 in the pathogenesis of HE. Rats were divided into 5 treatment groups; sham, bile duct ligation (BDL), HE, zinc protoporphyrin (ZnPP) and cobalt protoporphyrin (CoPP). The levels of HO-1 were examined by western blotting and quantitative real-time PCR (qRT-PCR). Serum levels of carboxyhemoglobin (COHb), ammonia levels in the plasma and brain, brain water content and portal vein pressure (PVP) were also quantified. Aquaporin-4 expression levels were measured by immunohistochemistry and qRT-PCR. The results demonstrated that the levels of HO-1 in the brain and the serum levels of COHb were significantly increased in the HE group compared with the BDL group. Brain water content, PVP and ammonia levels in the plasma and brain were increased in the HE and CoPP groups; however, these were reduced following the treatment with ZnPP. The levels of AQP-4 expression and oxidative stress in the brain were reduced following treatment with ZnPP and increased following treatment with CoPP. In conclusion, following the inhibition of HO-1 expression, treatment with ZnPP improved HE due to reducing the expression levels of AQP-4 and oxidative stress. Therefore, ZnPP treatment may represent a novel therapeutic approach for HE.

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

Cited by 37 publications

References 109 publications

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

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

Pharmacological and Clinical Aspects of Heme Oxygenase

Role of the heme oxygenase/carbon monoxide pathway in the pathogenesis and prevention of hepatic encephalopathy

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