Calpain Inhibition Protected Spinal Cord Motoneurons against 1-methyl-4-phenylpyridinium ion and Rotenone
Identifieur interne : 000705 ( Pmc/Checkpoint ); précédent : 000704; suivant : 000706Calpain Inhibition Protected Spinal Cord Motoneurons against 1-methyl-4-phenylpyridinium ion and Rotenone
Auteurs : Supriti Samantaray [États-Unis] ; Varduhi H. Knaryan [États-Unis] ; Charlene Le Gal [France] ; Swapan K. Ray [États-Unis] ; Naren L. Banik [États-Unis]Source :
- Neuroscience [ 0306-4522 ] ; 2011.
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 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 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:
DOI: 10.1016/j.neuroscience.2011.06.007
PubMed: 21723922
PubMed Central: 3166419
Affiliations:
- France, États-Unis
- Caroline du Sud, Nouvelle-Aquitaine, Poitou-Charentes
- Poitiers
- Université de Poitiers
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:3166419Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Calpain Inhibition Protected Spinal Cord Motoneurons against 1-methyl-4-phenylpyridinium ion and Rotenone</title>
<author><name sortKey="Samantaray, Supriti" sort="Samantaray, Supriti" uniqKey="Samantaray S" first="Supriti" last="Samantaray">Supriti Samantaray</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Knaryan, Varduhi H" sort="Knaryan, Varduhi H" uniqKey="Knaryan V" first="Varduhi H." last="Knaryan">Varduhi H. Knaryan</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Le Gal, Charlene" sort="Le Gal, Charlene" uniqKey="Le Gal C" first="Charlene" last="Le Gal">Charlene Le Gal</name>
<affiliation wicri:level="4"><nlm:aff id="A2">Université de Poitiers, Department of Basic and Applied Sciences, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université de Poitiers, Department of Basic and Applied Sciences, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex</wicri:regionArea>
<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, Swapan K" sort="Ray, Swapan K" uniqKey="Ray S" first="Swapan K." last="Ray">Swapan K. Ray</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Banik, Naren L" sort="Banik, Naren L" uniqKey="Banik N" first="Naren L." last="Banik">Naren L. Banik</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21723922</idno>
<idno type="pmc">3166419</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166419</idno>
<idno type="RBID">PMC:3166419</idno>
<idno type="doi">10.1016/j.neuroscience.2011.06.007</idno>
<date when="2011">2011</date>
<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>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Calpain Inhibition Protected Spinal Cord Motoneurons against 1-methyl-4-phenylpyridinium ion and Rotenone</title>
<author><name sortKey="Samantaray, Supriti" sort="Samantaray, Supriti" uniqKey="Samantaray S" first="Supriti" last="Samantaray">Supriti Samantaray</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Knaryan, Varduhi H" sort="Knaryan, Varduhi H" uniqKey="Knaryan V" first="Varduhi H." last="Knaryan">Varduhi H. Knaryan</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Le Gal, Charlene" sort="Le Gal, Charlene" uniqKey="Le Gal C" first="Charlene" last="Le Gal">Charlene Le Gal</name>
<affiliation wicri:level="4"><nlm:aff id="A2">Université de Poitiers, Department of Basic and Applied Sciences, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université de Poitiers, Department of Basic and Applied Sciences, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex</wicri:regionArea>
<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, Swapan K" sort="Ray, Swapan K" uniqKey="Ray S" first="Swapan K." last="Ray">Swapan K. Ray</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Banik, Naren L" sort="Banik, Naren L" uniqKey="Banik N" first="Naren L." last="Banik">Naren L. Banik</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Neuroscience</title>
<idno type="ISSN">0306-4522</idno>
<idno type="eISSN">1873-7544</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">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 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 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.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="en"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">7605074</journal-id>
<journal-id journal-id-type="pubmed-jr-id">6087</journal-id>
<journal-id journal-id-type="nlm-ta">Neuroscience</journal-id>
<journal-title-group><journal-title>Neuroscience</journal-title>
</journal-title-group>
<issn pub-type="ppub">0306-4522</issn>
<issn pub-type="epub">1873-7544</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21723922</article-id>
<article-id pub-id-type="pmc">3166419</article-id>
<article-id pub-id-type="doi">10.1016/j.neuroscience.2011.06.007</article-id>
<article-id pub-id-type="manuscript">NIHMS307645</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Calpain Inhibition Protected Spinal Cord Motoneurons against 1-methyl-4-phenylpyridinium ion and Rotenone</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Samantaray</surname>
<given-names>Supriti</given-names>
</name>
<xref rid="A1" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Knaryan</surname>
<given-names>Varduhi H.</given-names>
</name>
<xref rid="A1" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Le Gal</surname>
<given-names>Charlene</given-names>
</name>
<xref rid="A2" ref-type="aff">b</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ray</surname>
<given-names>Swapan K.</given-names>
</name>
<xref rid="A3" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Banik</surname>
<given-names>Naren L.</given-names>
</name>
<xref rid="A1" ref-type="aff">a</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>a</label>
Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, P.O. Box 250606, Charleston, SC 29425, USA</aff>
<aff id="A2"><label>b</label>
Université de Poitiers, Department of Basic and Applied Sciences, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France</aff>
<aff id="A3"><label>c</label>
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Corresponding author. Tel: +1-843-792-7594; fax: 1-843-792-8626. <email>baniknl@musc.edu</email>
(N. L. Banik)</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>9</day>
<month>7</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>22</day>
<month>6</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><day>29</day>
<month>9</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>29</day>
<month>9</month>
<year>2012</year>
</pub-date>
<volume>192</volume>
<fpage>263</fpage>
<lpage>274</lpage>
<abstract><p id="P1">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 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 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.</p>
</abstract>
<kwd-group><kwd>calpain</kwd>
<kwd>caspase-3</kwd>
<kwd>calpeptin</kwd>
<kwd>parkinsonian toxicants</kwd>
<kwd>spinal motoneuronal cells</kwd>
</kwd-group>
<funding-group><award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS062327-01A2 || NS</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
<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, Supriti" sort="Samantaray, Supriti" uniqKey="Samantaray S" first="Supriti" last="Samantaray">Supriti Samantaray</name>
</region>
<name sortKey="Banik, Naren L" sort="Banik, Naren L" uniqKey="Banik N" first="Naren L." last="Banik">Naren L. Banik</name>
<name sortKey="Knaryan, Varduhi H" sort="Knaryan, Varduhi H" uniqKey="Knaryan V" first="Varduhi H." last="Knaryan">Varduhi H. Knaryan</name>
<name sortKey="Ray, Swapan K" sort="Ray, Swapan K" uniqKey="Ray S" first="Swapan K." last="Ray">Swapan K. Ray</name>
</country>
<country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Le Gal, Charlene" sort="Le Gal, Charlene" uniqKey="Le Gal C" first="Charlene" last="Le Gal">Charlene Le Gal</name>
</region>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000705 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 000705 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= Pmc |étape= Checkpoint |type= RBID |clé= PMC:3166419 |texte= Calpain Inhibition Protected Spinal Cord Motoneurons against 1-methyl-4-phenylpyridinium ion and Rotenone }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:21723922" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a ParkinsonFranceV1
![]() | This area was generated with Dilib version V0.6.29. | ![]() |