ParkinsonFranceV1, Main, Exploration, bibRecordById, PMC:3166419

CALPAIN INHIBITION PROTECTED SPINAL CORD MOTONEURONS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM ION AND ROTENONE

Identifieur interne : 001854 ( Main/Exploration ); précédent : 001853; suivant : 001855

CALPAIN INHIBITION PROTECTED SPINAL CORD MOTONEURONS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM ION AND ROTENONE

Auteurs : S. Samantaray [États-Unis] ; V. H. Knaryan [États-Unis] ; C. Le Gal [France] ; S. K. Ray [États-Unis] ; N. L. Banik [États-Unis]

Source :

Neuroscience [ 0306-4522 ] ; 2011.

RBID : Pascal:12-0016553

Descripteurs français

Pascal (Inist)
- Calpain, Moelle épinière, Neurone moteur, Caspase, Maladie de Parkinson, Roténone.

English descriptors

KwdEn :
- Calpain, Caspase, Motor neuron, Parkinson disease, Rotenone, Spinal cord.

Abstract

Parkinson's disease (PD), characterized by selective midbrain nigrostriatal dopaminergic degeneration, is consistently associated with moderate systemic mitochondrial dysfunction. Downstream degeneration of spinal cord has also been suggested in PD, although the mechanisms have not been much investigated. In the present study, two mitochondrial toxicants, 1-methyl-4-phenylpyridinium ion (MPP⁺) and rotenone were tested in ventral spinal cord (VSC 4.1) motoneuronal cells. Cell death was assessed by morphological and biochemical means to discern a lower apoptosis-inducing concentration and lethal concentration of 50% cell death (LC₅₀), which were subsequently compared in further cytoprotection experiments. Mitochondrial toxicants dose-dependently induced increase in intracellular free Ca²⁺ level, which was conducive for increased expression and activities of Ca²⁺-activated neutral protease calpain and downstream caspase-3. Thus, mitochondrial damage triggered apoptotic mechanisms in spinal cord motoneurons. Inhibition of calpain by calpeptin significantly attenuated damaging effects of MPP⁺ and rotenone on motoneurons, especially at low apoptosis-inducing concentrations of toxicants and partly at their LC₅₀, as demonstrated by absence of DNA ladder formation and decrease in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells. Cytoprotection by calpeptin was observed with marked decreases in Bax: Bcl-2 ratio and activities of calpain and caspase-3, which affirmed the role of mitochondrial dysfunction and involvement of intrinsic pathway in mediation of apoptosis. These findings strongly suggested that parkinsonian toxicants MPP⁺ and rotenone at low doses induced cascade of cell-damaging effects in spinal cord motoneurons, thus, highlighting the possibility of induction of apoptotic mechanisms in these cells, when subjected to mitochondrial stress. Cytoprotection rendered by calpeptin further validated the involvement of calpain in apoptosis and suggested calpain inhibition as a potential neuroprotective strategy.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166419

Affiliations:

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">CALPAIN INHIBITION PROTECTED SPINAL CORD MOTONEURONS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM ION AND ROTENONE</title>
<author><name sortKey="Samantaray, S" sort="Samantaray, S" uniqKey="Samantaray S" first="S." last="Samantaray">S. Samantaray</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, PO Box 250606</s1>
<s2>Charles-ton, SC 29425</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Knaryan, V H" sort="Knaryan, V H" uniqKey="Knaryan V" first="V. H." last="Knaryan">V. H. Knaryan</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, PO Box 250606</s1>
<s2>Charles-ton, SC 29425</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Le Gal, C" sort="Le Gal, C" uniqKey="Le Gal C" first="C." last="Le Gal">C. Le Gal</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Basic and Applied Sciences, Université de Poitiers, 40 Avenue du Recteur Pineau</s1>
<s2>86022 Poitiers</s2>
<s3>FRA</s3>
<sZ>3 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region>
<region type="old region" nuts="2">Poitou-Charentes</region>
<settlement type="city">Poitiers</settlement>
</placeName>
<orgName type="university">Université de Poitiers</orgName>
</affiliation>
</author>
<author><name sortKey="Ray, S K" sort="Ray, S K" uniqKey="Ray S" first="S. K." last="Ray">S. K. Ray</name>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road</s1>
<s2>Columbia, SC 29209</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Banik, N L" sort="Banik, N L" uniqKey="Banik N" first="N. L." last="Banik">N. L. Banik</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, PO Box 250606</s1>
<s2>Charles-ton, SC 29425</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">12-0016553</idno>
<date when="2011">2011</date>
<idno type="stanalyst">PASCAL 12-0016553 INIST</idno>
<idno type="RBID">Pascal:12-0016553</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000311</idno>
<idno type="wicri:Area/PascalFrancis/Curation">001010</idno>
<idno type="wicri:Area/PascalFrancis/Checkpoint">000361</idno>
<idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000361</idno>
<idno type="wicri:doubleKey">0306-4522:2011:Samantaray S:calpain:inhibition:protected</idno>
<idno type="wicri:Area/Main/Merge">001951</idno>
<idno type="wicri:source">PMC</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166419</idno>
<idno type="RBID">PMC:3166419</idno>
<idno type="wicri:Area/Pmc/Corpus">000399</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000399</idno>
<idno type="wicri:Area/Pmc/Curation">000396</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000396</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000705</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000705</idno>
<idno type="wicri:Area/Ncbi/Merge">000D48</idno>
<idno type="wicri:Area/Ncbi/Curation">000D48</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000D48</idno>
<idno type="wicri:doubleKey">0306-4522:2011:Samantaray S:calpain:inhibition:protected</idno>
<idno type="wicri:Area/Main/Merge">001690</idno>
<idno type="wicri:Area/Main/Curation">001854</idno>
<idno type="wicri:Area/Main/Exploration">001854</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">CALPAIN INHIBITION PROTECTED SPINAL CORD MOTONEURONS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM ION AND ROTENONE</title>
<author><name sortKey="Samantaray, S" sort="Samantaray, S" uniqKey="Samantaray S" first="S." last="Samantaray">S. Samantaray</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, PO Box 250606</s1>
<s2>Charles-ton, SC 29425</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Knaryan, V H" sort="Knaryan, V H" uniqKey="Knaryan V" first="V. H." last="Knaryan">V. H. Knaryan</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, PO Box 250606</s1>
<s2>Charles-ton, SC 29425</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Le Gal, C" sort="Le Gal, C" uniqKey="Le Gal C" first="C." last="Le Gal">C. Le Gal</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Basic and Applied Sciences, Université de Poitiers, 40 Avenue du Recteur Pineau</s1>
<s2>86022 Poitiers</s2>
<s3>FRA</s3>
<sZ>3 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region>
<region type="old region" nuts="2">Poitou-Charentes</region>
<settlement type="city">Poitiers</settlement>
</placeName>
<orgName type="university">Université de Poitiers</orgName>
</affiliation>
</author>
<author><name sortKey="Ray, S K" sort="Ray, S K" uniqKey="Ray S" first="S. K." last="Ray">S. K. Ray</name>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road</s1>
<s2>Columbia, SC 29209</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Banik, N L" sort="Banik, N L" uniqKey="Banik N" first="N. L." last="Banik">N. L. Banik</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, PO Box 250606</s1>
<s2>Charles-ton, SC 29425</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Neuroscience</title>
<title level="j" type="abbreviated">Neuroscience</title>
<idno type="ISSN">0306-4522</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Neuroscience</title>
<title level="j" type="abbreviated">Neuroscience</title>
<idno type="ISSN">0306-4522</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Calpain</term>
<term>Caspase</term>
<term>Motor neuron</term>
<term>Parkinson disease</term>
<term>Rotenone</term>
<term>Spinal cord</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Calpain</term>
<term>Moelle épinière</term>
<term>Neurone moteur</term>
<term>Caspase</term>
<term>Maladie de Parkinson</term>
<term>Roténone</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Parkinson's disease (PD), characterized by selective midbrain nigrostriatal dopaminergic degeneration, is consistently associated with moderate systemic mitochondrial dysfunction. Downstream degeneration of spinal cord has also been suggested in PD, although the mechanisms have not been much investigated. In the present study, two mitochondrial toxicants, 1-methyl-4-phenylpyridinium ion (MPP<sup>+</sup>
) and rotenone were tested in ventral spinal cord (VSC 4.1) motoneuronal cells. Cell death was assessed by morphological and biochemical means to discern a lower apoptosis-inducing concentration and lethal concentration of 50% cell death (LC<sub>50</sub>
), which were subsequently compared in further cytoprotection experiments. Mitochondrial toxicants dose-dependently induced increase in intracellular free Ca<sup>2+</sup>
 level, which was conducive for increased expression and activities of Ca<sup>2+</sup>
-activated neutral protease calpain and downstream caspase-3. Thus, mitochondrial damage triggered apoptotic mechanisms in spinal cord motoneurons. Inhibition of calpain by calpeptin significantly attenuated damaging effects of MPP<sup>+</sup>
 and rotenone on motoneurons, especially at low apoptosis-inducing concentrations of toxicants and partly at their LC<sub>50</sub>
, as demonstrated by absence of DNA ladder formation and decrease in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells. Cytoprotection by calpeptin was observed with marked decreases in Bax: Bcl-2 ratio and activities of calpain and caspase-3, which affirmed the role of mitochondrial dysfunction and involvement of intrinsic pathway in mediation of apoptosis. These findings strongly suggested that parkinsonian toxicants MPP<sup>+</sup>
 and rotenone at low doses induced cascade of cell-damaging effects in spinal cord motoneurons, thus, highlighting the possibility of induction of apoptotic mechanisms in these cells, when subjected to mitochondrial stress. Cytoprotection rendered by calpeptin further validated the involvement of calpain in apoptosis and suggested calpain inhibition as a potential neuroprotective strategy.</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>États-Unis</li>
</country>
<region><li>Caroline du Sud</li>
<li>Nouvelle-Aquitaine</li>
<li>Poitou-Charentes</li>
</region>
<settlement><li>Poitiers</li>
</settlement>
<orgName><li>Université de Poitiers</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Caroline du Sud"><name sortKey="Samantaray, S" sort="Samantaray, S" uniqKey="Samantaray S" first="S." last="Samantaray">S. Samantaray</name>
</region>
<name sortKey="Banik, N L" sort="Banik, N L" uniqKey="Banik N" first="N. L." last="Banik">N. L. Banik</name>
<name sortKey="Knaryan, V H" sort="Knaryan, V H" uniqKey="Knaryan V" first="V. H." last="Knaryan">V. H. Knaryan</name>
<name sortKey="Ray, S K" sort="Ray, S K" uniqKey="Ray S" first="S. K." last="Ray">S. K. Ray</name>
</country>
<country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Le Gal, C" sort="Le Gal, C" uniqKey="Le Gal C" first="C." last="Le Gal">C. Le Gal</name>
</region>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001854 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001854 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Sante
   |area=    ParkinsonFranceV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     Pascal:12-0016553
   |texte=   CALPAIN INHIBITION PROTECTED SPINAL CORD MOTONEURONS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM ION AND ROTENONE
}}

This area was generated with Dilib version V0.6.29.
Data generation: Wed May 17 19:46:39 2017. Site generation: Mon Mar 4 15:48:15 2024

La maladie de Parkinson en France (serveur d'exploration)

CALPAIN INHIBITION PROTECTED SPINAL CORD MOTONEURONS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM ION AND ROTENONE

CALPAIN INHIBITION PROTECTED SPINAL CORD MOTONEURONS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM ION AND ROTENONE

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

	La maladie de Parkinson en France (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.