Astroglia overexpressing heme oxygenase‐1 predispose co‐cultured PC12 cells to oxidative injury
Identifieur interne : 002610 ( Main/Exploration ); précédent : 002609; suivant : 002611Astroglia overexpressing heme oxygenase‐1 predispose co‐cultured PC12 cells to oxidative injury
Auteurs : Linyang Song [Canada] ; Wei Song [Canada] ; Hyman M. Schipper [Canada]Source :
- Journal of Neuroscience Research [ 0360-4012 ] ; 2007-08-01.
English descriptors
Abstract
The mechanisms responsible for the progressive degeneration of dopaminergic neurons and pathologic iron deposition in the substantia nigra pars compacta of patients with Parkinson's disease (PD) remain unclear. Heme oxygenase‐1 (HO‐1), the rate‐limiting enzyme in the oxidative degradation of heme to ferrous iron, carbon monoxide, and biliverdin, is upregulated in affected PD astroglia and may contribute to abnormal mitochondrial iron sequestration in these cells. To determine whether glial HO‐1 hyper‐expression is toxic to neuronal compartments, we co‐cultured dopaminergic PC12 cells atop monolayers of human (h) HO‐1 transfected, sham‐transfected, or non‐transfected primary rat astroglia. We observed that PC12 cells grown atop hHO‐1 transfected astrocytes, but not the astroglia themselves, were significantly more susceptible to dopamine (1 μM) + H2O2 (1 μM)‐induced death (assessed by nuclear ethidium monoazide bromide staining and anti‐tyrosine hydroxylase immunofluorescence microscopy) relative to control preparations. In the experimental group, PC12 cell death was attenuated significantly by the administration of the HO inhibitor, SnMP (1.5 μM), the antioxidant, ascorbate (200 μM), or the iron chelators, deferoxamine (400 μM), and phenanthroline (100 μM). Exposure to conditioned media derived from HO‐1 transfected astrocytes also augmented PC12 cell killing in response to dopamine (1 μM) + H2O2 (1 μM) relative to control media. In PD brain, overexpression of HO‐1 in nigral astroglia and accompanying iron liberation may facilitate the bioactivation of dopamine to neurotoxic free radical intermediates and predispose nearby neuronal constituents to oxidative damage. © 2007 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/jnr.21367
Affiliations:
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Res.</title><idno type="ISSN">0360-4012</idno><idno type="eISSN">1097-4547</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-08-01">2007-08-01</date><biblScope unit="volume">85</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="2186">2186</biblScope><biblScope unit="page" to="2195">2195</biblScope></imprint><idno type="ISSN">0360-4012</idno></series><idno type="istex">E9A3E04E1FBE1BEEC525B5C3AC80341EE69338BD</idno><idno type="DOI">10.1002/jnr.21367</idno><idno type="ArticleID">JNR21367</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0360-4012</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>heme oxygenase‐1</term><term>iron</term><term>oxidative stress</term><term>rat astrocyte</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The mechanisms responsible for the progressive degeneration of dopaminergic neurons and pathologic iron deposition in the substantia nigra pars compacta of patients with Parkinson's disease (PD) remain unclear. Heme oxygenase‐1 (HO‐1), the rate‐limiting enzyme in the oxidative degradation of heme to ferrous iron, carbon monoxide, and biliverdin, is upregulated in affected PD astroglia and may contribute to abnormal mitochondrial iron sequestration in these cells. To determine whether glial HO‐1 hyper‐expression is toxic to neuronal compartments, we co‐cultured dopaminergic PC12 cells atop monolayers of human (h) HO‐1 transfected, sham‐transfected, or non‐transfected primary rat astroglia. We observed that PC12 cells grown atop hHO‐1 transfected astrocytes, but not the astroglia themselves, were significantly more susceptible to dopamine (1 μM) + H2O2 (1 μM)‐induced death (assessed by nuclear ethidium monoazide bromide staining and anti‐tyrosine hydroxylase immunofluorescence microscopy) relative to control preparations. In the experimental group, PC12 cell death was attenuated significantly by the administration of the HO inhibitor, SnMP (1.5 μM), the antioxidant, ascorbate (200 μM), or the iron chelators, deferoxamine (400 μM), and phenanthroline (100 μM). Exposure to conditioned media derived from HO‐1 transfected astrocytes also augmented PC12 cell killing in response to dopamine (1 μM) + H2O2 (1 μM) relative to control media. In PD brain, overexpression of HO‐1 in nigral astroglia and accompanying iron liberation may facilitate the bioactivation of dopamine to neurotoxic free radical intermediates and predispose nearby neuronal constituents to oxidative damage. © 2007 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Québec</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Song, Linyang" sort="Song, Linyang" uniqKey="Song L" first="Linyang" last="Song">Linyang Song</name></noRegion><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name><name sortKey="Song, Linyang" sort="Song, Linyang" uniqKey="Song L" first="Linyang" last="Song">Linyang Song</name><name sortKey="Song, Wei" sort="Song, Wei" uniqKey="Song W" first="Wei" last="Song">Wei Song</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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