Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The successful prevention of hydrogen peroxide-induced alveolar permeability alterations and cell injury by transferrin-catalase conjugate is described in this study. Permeability alterations and cell injury were induced in cultured alveolar epithelial monolayers by hydrogen peroxide. Transepithelial transport of a permeability marker, [14C] mannitol, and cellular nuclear fluorescence of a membrane integrity indicator, propidium iodide, were used to quantitate epithelial permeability and damage respectively. Hydrogen peroxide (0.1 - 10 mM) induced a dose-dependent increase in both alveolar permeability and cellular damage; however, the oxidant effect on monolayer permeability did not require prior cell damage. Electron spin resonance measurements using the spin trap 5,5-dimethyl-l-pyrroline-N-oxide indicated the formation of hydroxyl radicals in hydrogen peroxide-treated cells. Chelation of the cellular pool of iron by deferoxamine inhibited radical formation and helped protect the cells from oxidative changes. Prior treatment of the cells with catalase (0.1 U-10 U/ml) had minimal protective effects on cell injury and permeability alterations. In contrast, transferrin-catalase conjugate, at the same concentration range, exhibited much improved protective effects on the cells in response to oxidant stress. This enhanced protection was found to correlate well with an increase in cellular uptake of the enzyme conjugate via the transferrin receptor endocytosis pathway. Effective protection by the enzyme conjugate was shown to require both the antioxidant enzyme moiety and the cognate moiety for the cell surface receptor. These findings indicate the potential therapeutic merit of transferrin-catalase conjugate for the treatment of pathological processes in the lung, whenever oxidative stress is involved.
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PMID:Protection against oxidative injury and permeability alteration in cultured alveolar epithelium by transferrin-catalase conjugate. 861 42

1-Methyl-4-phenylpyridinium (MPP(+)) is a neurotoxin used in cellular models of Parkinson's Disease. Although intracellular iron plays a crucial role in MPP(+)-induced apoptosis, the molecular signalling mechanisms linking iron, reactive oxygen species (ROS) and apoptosis are still unknown. We investigated these aspects using cerebellar granule neurons (CGNs) and human SH-SY5Y neuroblastoma cells. MPP(+) enhanced caspase 3 activity after 24 h with significant increases as early as 12 h after treatment of cells. Pre-treatment of CGNs and neuroblastoma cells with the metalloporphyrin antioxidant enzyme mimic, Fe(III)tetrakis(4-benzoic acid)porphyrin (FeTBAP), completely prevented the MPP(+)-induced caspase 3 activity as did overexpression of glutathione peroxidase (GPx1) and pre-treatment with a lipophilic, cell-permeable iron chelator [N, N '-bis-(2-hydroxybenzyl)ethylenediamine-N, N '-diacetic acid, HBED]. MPP(+) treatment increased the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labelling)-positive cells which was completely blocked by pre-treatment with FeTBAP. MPP(+) treatment significantly decreased the aconitase and mitochondrial complex I activities; pre-treatment with FeTBAP, HBED and GPx1 overexpression reversed this effect. MPP(+) treatment increased the intracellular oxidative stress by 2-3-fold, as determined by oxidation of dichlorodihydrofluorescein and dihydroethidium (hydroethidine). These effects were reversed by pre-treatment of cells with FeTBAP and HBED and by GPx1 overexpression. MPP(+)-treatment enhanced the cell-surface transferrin receptor (TfR) expression, suggesting a role for TfR-induced iron uptake in MPP(+) toxicity. Treatment of cells with anti-TfR antibody (IgA class) inhibited MPP(+)-induced caspase activation. Inhibition of nitric oxide synthase activity did not affect caspase 3 activity, apoptotic cell death or ROS generation by MPP(+). Overall, these results suggest that MPP(+)-induced cell death in CGNs and neuroblastoma cells proceeds via apoptosis and involves mitochondrial release of ROS and TfR-dependent iron.
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PMID:1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant generation: role of transferrin-receptor-dependent iron and hydrogen peroxide. 1252 38