ParkinsonCanadaV1, France, Analysis, bibRecord, 000143

Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment

Identifieur interne : 000143 ( France/Analysis ); précédent : 000142; suivant : 000144

Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment

Auteurs : WEI SONG [Canada] ; Hillel Zukor [Canada] ; Shih-Hsiung Lin [Canada] ; Adrienne Liberman [Canada] ; Ayda Tavitian [Canada] ; Jeannie Mui [Canada] ; Hojatollah Vali [Canada] ; Carine Fillebeen [Canada] ; Kostas Pantopoulos [Canada] ; Ting-Di Wu [France] ; Jean-Luc Guerquin-Kern [France] ; Hyman M. Schipper [Canada]

Source :

Journal of neurochemistry [ 0022-3042 ] ; 2012.

RBID : Pascal:12-0412033

Descripteurs français

Pascal (Inist)
- Encéphale, Fer, Système nerveux central, Stress, Protéine liaison, Hème, Induction, Culture primaire, Démence d'Alzheimer, Transferrine, Mitochondrie, Maladie de Parkinson, Méthode dynamique, Ion, Souris, Homme.
Wicri :
- topic : Fer, Homme.

English descriptors

KwdEn :
- Alzheimer disease, Binding protein, Central nervous system, Dynamic method, Encephalon, Heme, Human, Induction, Ions, Iron, Mitochondria, Mouse, Parkinson disease, Primary culture, Stress, Transferrin.

Abstract

The mechanisms responsible for pathological iron deposition in the aging and degenerating mammalian CNS remain poorly understood. The stress protein, HO-1 mediates the degradation of cellular heme to biliverdin/bilirubin, free iron, and CO and is up-regulated in the brains of persons with Alzheimer's disease and Parkinson's disease. HO-1 induction in primary astroglial cultures promotes deposition of non-transferrin iron, mitochondrial damage and macroautophagy, and predisposes cocultured neuronal elements to oxidative injury. To gain a better appreciation of the role of glial HO-1 in vivo, we probed for aberrant brain iron deposition using Perls' method and dynamic secondary ion mass spectrometry in novel, conditional GFAP.HMOX1 transgenic mice that selectively over-express human HO-1 in the astrocytic compartment. At 48 weeks, the GFAP.HMOX1 mice exhibited increased deposits of glial iron in hippocampus and other subcortical regions without overt changes in iron-regulatory and iron-binding proteins relative to age-matched wild-type animals. Dynamic secondary ion mass spectrometry revealed abundant FeO^- signals in the transgenic, but not wild-type, mouse brain that colocalized to degenerate mitochondria and osmiophilic cytoplasmic inclusions (macroautophagy) documented by TEM. Sustained up-regulation of HO-1 in astrocytes promotes pathological brain iron deposition and oxidative mitochondrial damage characteristic of Alzheimer's disease-affected neural tissues. Curtailment of glial HO-1 hyperactivity may limit iron-mediated cytotoxicity in aging and degenerating neural tissues.

Affiliations:

Links to Exploration step

Pascal:12-0412033

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment</title>
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<author><name sortKey="Vali, Hojatollah" sort="Vali, Hojatollah" uniqKey="Vali H" first="Hojatollah" last="Vali">Hojatollah Vali</name>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Facility for Electron Microscopy Research, McGill University</s1>
<s2>Montreal, Quebec</s2>
<s3>CAN</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université McGill</orgName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Anatomy and Cell Biolagy, Faculty of Medicine, McGill University</s1>
<s2>Montreal, Quebec</s2>
<s3>CAN</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université McGill</orgName>
</affiliation>
</author>
<author><name sortKey="Fillebeen, Carine" sort="Fillebeen, Carine" uniqKey="Fillebeen C" first="Carine" last="Fillebeen">Carine Fillebeen</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Lady Davis Institute, Jewish General Hospital</s1>
<s2>Montreal, Quebec</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Montreal, Quebec</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pantopoulos, Kostas" sort="Pantopoulos, Kostas" uniqKey="Pantopoulos K" first="Kostas" last="Pantopoulos">Kostas Pantopoulos</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Lady Davis Institute, Jewish General Hospital</s1>
<s2>Montreal, Quebec</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Montreal, Quebec</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department of Medicine, McGill University</s1>
<s2>Montreal, Quebec</s2>
<s3>CAN</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université McGill</orgName>
</affiliation>
</author>
<author><name sortKey="Wu, Ting Di" sort="Wu, Ting Di" uniqKey="Wu T" first="Ting-Di" last="Wu">Ting-Di Wu</name>
<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM</s1>
<s2>U759, Orsay</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Orsay</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Laboratoire de Microscopie Ionique, Institut Curie</s1>
<s2>Orsay</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Orsay</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Guerquin Kern, Jean Luc" sort="Guerquin Kern, Jean Luc" uniqKey="Guerquin Kern J" first="Jean-Luc" last="Guerquin-Kern">Jean-Luc Guerquin-Kern</name>
<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM</s1>
<s2>U759, Orsay</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Orsay</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Laboratoire de Microscopie Ionique, Institut Curie</s1>
<s2>Orsay</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Orsay</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Lady Davis Institute, Jewish General Hospital</s1>
<s2>Montreal, Quebec</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Montreal, Quebec</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Neurology and Neurosurgery, McGill University</s1>
<s2>Montreal, Quebec</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université McGill</orgName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of neurochemistry</title>
<title level="j" type="abbreviated">J. neurochem.</title>
<idno type="ISSN">0022-3042</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of neurochemistry</title>
<title level="j" type="abbreviated">J. neurochem.</title>
<idno type="ISSN">0022-3042</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alzheimer disease</term>
<term>Binding protein</term>
<term>Central nervous system</term>
<term>Dynamic method</term>
<term>Encephalon</term>
<term>Heme</term>
<term>Human</term>
<term>Induction</term>
<term>Ions</term>
<term>Iron</term>
<term>Mitochondria</term>
<term>Mouse</term>
<term>Parkinson disease</term>
<term>Primary culture</term>
<term>Stress</term>
<term>Transferrin</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Encéphale</term>
<term>Fer</term>
<term>Système nerveux central</term>
<term>Stress</term>
<term>Protéine liaison</term>
<term>Hème</term>
<term>Induction</term>
<term>Culture primaire</term>
<term>Démence d'Alzheimer</term>
<term>Transferrine</term>
<term>Mitochondrie</term>
<term>Maladie de Parkinson</term>
<term>Méthode dynamique</term>
<term>Ion</term>
<term>Souris</term>
<term>Homme</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Fer</term>
<term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The mechanisms responsible for pathological iron deposition in the aging and degenerating mammalian CNS remain poorly understood. The stress protein, HO-1 mediates the degradation of cellular heme to biliverdin/bilirubin, free iron, and CO and is up-regulated in the brains of persons with Alzheimer's disease and Parkinson's disease. HO-1 induction in primary astroglial cultures promotes deposition of non-transferrin iron, mitochondrial damage and macroautophagy, and predisposes cocultured neuronal elements to oxidative injury. To gain a better appreciation of the role of glial HO-1 in vivo, we probed for aberrant brain iron deposition using Perls' method and dynamic secondary ion mass spectrometry in novel, conditional GFAP.HMOX1 transgenic mice that selectively over-express human HO-1 in the astrocytic compartment. At 48 weeks, the GFAP.HMOX1 mice exhibited increased deposits of glial iron in hippocampus and other subcortical regions without overt changes in iron-regulatory and iron-binding proteins relative to age-matched wild-type animals. Dynamic secondary ion mass spectrometry revealed abundant FeO<sup>-</sup>
 signals in the transgenic, but not wild-type, mouse brain that colocalized to degenerate mitochondria and osmiophilic cytoplasmic inclusions (macroautophagy) documented by TEM. Sustained up-regulation of HO-1 in astrocytes promotes pathological brain iron deposition and oxidative mitochondrial damage characteristic of Alzheimer's disease-affected neural tissues. Curtailment of glial HO-1 hyperactivity may limit iron-mediated cytotoxicity in aging and degenerating neural tissues.</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>France</li>
</country>
<region><li>Québec</li>
</region>
<settlement><li>Montréal</li>
<li>Orsay</li>
</settlement>
<orgName><li>Université McGill</li>
</orgName>
</list>
<tree><country name="Canada"><noRegion><name sortKey="Wei Song" sort="Wei Song" uniqKey="Wei Song" last="Wei Song">WEI SONG</name>
</noRegion>
<name sortKey="Fillebeen, Carine" sort="Fillebeen, Carine" uniqKey="Fillebeen C" first="Carine" last="Fillebeen">Carine Fillebeen</name>
<name sortKey="Liberman, Adrienne" sort="Liberman, Adrienne" uniqKey="Liberman A" first="Adrienne" last="Liberman">Adrienne Liberman</name>
<name sortKey="Lin, Shih Hsiung" sort="Lin, Shih Hsiung" uniqKey="Lin S" first="Shih-Hsiung" last="Lin">Shih-Hsiung Lin</name>
<name sortKey="Lin, Shih Hsiung" sort="Lin, Shih Hsiung" uniqKey="Lin S" first="Shih-Hsiung" last="Lin">Shih-Hsiung Lin</name>
<name sortKey="Mui, Jeannie" sort="Mui, Jeannie" uniqKey="Mui J" first="Jeannie" last="Mui">Jeannie Mui</name>
<name sortKey="Mui, Jeannie" sort="Mui, Jeannie" uniqKey="Mui J" first="Jeannie" last="Mui">Jeannie Mui</name>
<name sortKey="Pantopoulos, Kostas" sort="Pantopoulos, Kostas" uniqKey="Pantopoulos K" first="Kostas" last="Pantopoulos">Kostas Pantopoulos</name>
<name sortKey="Pantopoulos, Kostas" sort="Pantopoulos, Kostas" uniqKey="Pantopoulos K" first="Kostas" last="Pantopoulos">Kostas Pantopoulos</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="Tavitian, Ayda" sort="Tavitian, Ayda" uniqKey="Tavitian A" first="Ayda" last="Tavitian">Ayda Tavitian</name>
<name sortKey="Tavitian, Ayda" sort="Tavitian, Ayda" uniqKey="Tavitian A" first="Ayda" last="Tavitian">Ayda Tavitian</name>
<name sortKey="Vali, Hojatollah" sort="Vali, Hojatollah" uniqKey="Vali H" first="Hojatollah" last="Vali">Hojatollah Vali</name>
<name sortKey="Vali, Hojatollah" sort="Vali, Hojatollah" uniqKey="Vali H" first="Hojatollah" last="Vali">Hojatollah Vali</name>
<name sortKey="Zukor, Hillel" sort="Zukor, Hillel" uniqKey="Zukor H" first="Hillel" last="Zukor">Hillel Zukor</name>
<name sortKey="Zukor, Hillel" sort="Zukor, Hillel" uniqKey="Zukor H" first="Hillel" last="Zukor">Hillel Zukor</name>
</country>
<country name="France"><noRegion><name sortKey="Wu, Ting Di" sort="Wu, Ting Di" uniqKey="Wu T" first="Ting-Di" last="Wu">Ting-Di Wu</name>
</noRegion>
<name sortKey="Guerquin Kern, Jean Luc" sort="Guerquin Kern, Jean Luc" uniqKey="Guerquin Kern J" first="Jean-Luc" last="Guerquin-Kern">Jean-Luc Guerquin-Kern</name>
<name sortKey="Guerquin Kern, Jean Luc" sort="Guerquin Kern, Jean Luc" uniqKey="Guerquin Kern J" first="Jean-Luc" last="Guerquin-Kern">Jean-Luc Guerquin-Kern</name>
<name sortKey="Wu, Ting Di" sort="Wu, Ting Di" uniqKey="Wu T" first="Ting-Di" last="Wu">Ting-Di Wu</name>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson au Canada (serveur d'exploration)

Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment

Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment

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	La maladie de Parkinson au Canada (serveur d'exploration)
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