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Polyamidoamine dendrimer impairs mitochondrial oxidation in brain tissue
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Background: The potential nanocarrier polyamidoamine (PAMAM) generation 5 (G5-NH2) dendrimer has been shown to evoke lasting neuronal depolarization and cell death in a concentration-dependent manner. In this study we explored the early progression of G5-NH2 action in brain tissue on neuronal and astroglial cells.Results: In order to describe early mechanisms of G5-NH2 dendrimer action in brain tissue we assessed G5-NH2 trafficking, free intracellular Ca2+ and mitochondrial membrane potential (ΨMITO) changes in the rat hippocampal slice by microfluorimetry. With the help of fluorescent dye conjugated G5-NH2, we observed predominant appearance of the dendrimer in the plasma membrane of pyramidal neurons and glial cells within 30 min. Under this condition, G5-NH2 evoked robust intracellular Ca2+ enhancements and ΨMITO depolarization both in pyramidal neurons and astroglial cells. Intracellular Ca2+ enhancements clearly preceded ΨMITO depolarization in astroglial cells. Comparing activation dynamics, neurons and glia showed prevalence of lasting and transient ΨMITO depolarization, respectively. Transient as opposed to lasting ΨMITO changes to short-term G5-NH2 application suggested better survival of astroglia, as observed in the CA3 stratum radiatum area. We also showed that direct effect of G5-NH2 on astroglial ΨMITO was significantly enhanced by neuron-astroglia interaction, subsequent to G5-NH2 evoked neuronal activation.Conclusion: These findings indicate that the interaction of the PAMAM dendrimer with the plasma membrane leads to robust activation of neurons and astroglial cells, leading to mitochondrial depolarization. Distinguishable dynamics of mitochondrial depolarization in neurons and astroglia suggest that the enhanced mitochondrial depolarization followed by impaired oxidative metabolism of neurons may be the primary basis of neurotoxicity. © 2013 Nyitrai et al.; licensee BioMed Central Ltd.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10001104"> <a href="/gui2/?type=authors&mode=browse&sel=10001104" target="_blank">Nyitrai, G</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10001431"> <a href="/gui2/?type=authors&mode=browse&sel=10001431" target="_blank">Héja, L</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10008310"> <a href="/gui2/?type=authors&mode=browse&sel=10008310" target="_blank">Jablonkai, I</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10022719"> <a href="/gui2/?type=authors&mode=browse&sel=10022719" target="_blank">Pál, I</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10004542"> <a href="/gui2/?type=authors&mode=browse&sel=10004542" target="_blank">Visy, J</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10001101"> <a href="/gui2/?type=authors&mode=browse&sel=10001101" target="_blank">Kardos, J</a> </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;2305501" mtid="2305501" target="_blank">Polyamidoamine dendrimer impairs mitochondrial oxidation in brain tissue</a></div> <div class="pub-info"> <span class="journal-title">JOURNAL OF NANOBIOTECHNOLOGY</span> <span class="journal-volume">11</span> <span class="page"> Paper: 9 , 9 p. </span> <span class="year">(2013)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1186/1477-3155-11-9" target="_blank" href="https://doi.org/10.1186/1477-3155-11-9"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="5965" target="_blank" href="http://real.mtak.hu/5965"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000317644200001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000317644200001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84875688528" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84875688528"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="23556550" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23556550&dopt=Abstract"> PubMed </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:2305501 </span> <span class="status-holder"><span class="status-data status-APPROVED"> Nyilvános </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 28</span> | Független: 25 | Függő: 3 | Nem jelölt: 0 | WoS jelölt: 21 | Scopus jelölt: 22 | WoS/Scopus jelölt: 25 | DOI jelölt: 25 </div> </div> </div> </div><div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10001104"><a href="/gui2/?type=authors&mode=browse&sel=10001104" target="_blank">Nyitrai G (<span class="authorship-author-name">Nyitrai Gabriella</span> <span class="authorAux-mtmt"> </span>) </a> </span> <span class="author-affil"><span title="MTA Természettudományi Kutatóközpont">MTA TTK</span>/Molekuláris Farmakológiai Intézet; <span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/<span title="Szerves Kémiai Intézet">SZKI</span>/Funkcionális Farmakológiai Csoport</span> ; <span class="author-name" mtid="10001431"><a href="/gui2/?type=authors&mode=browse&sel=10001431" target="_blank">Héja L (<span class="authorship-author-name">Héja László</span> <span class="authorAux-mtmt"> Neurokémia</span>) </a> </span> <span class="author-affil"><span title="MTA Természettudományi Kutatóközpont">MTA TTK</span>/Molekuláris Farmakológiai Intézet; <span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/<span title="Szerves Kémiai Intézet">SZKI</span>/Funkcionális Farmakológiai Csoport</span> ; <span class="author-name" mtid="10008310"><a href="/gui2/?type=authors&mode=browse&sel=10008310" target="_blank">Jablonkai I (<span class="authorship-author-name">Jablonkai István</span> <span class="authorAux-mtmt"> Szerves kémia</span>) </a> </span> <span class="author-affil"><span title="MTA Természettudományi Kutatóközpont">MTA TTK</span>/Molekuláris Farmakológiai Intézet; <span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/<span title="Szerves Kémiai Intézet">SZKI</span>/Funkcionális Farmakológiai Csoport</span> ; <span class="author-name" mtid="10022719"><a href="/gui2/?type=authors&mode=browse&sel=10022719" target="_blank">Pál I (<span class="authorship-author-name">Pál Ildikó</span> <span class="authorAux-mtmt"> Kémia</span>) </a> </span> <span class="author-affil"><span title="MTA Természettudományi Kutatóközpont">MTA TTK</span>/Molekuláris Farmakológiai Intézet; <span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/<span title="Szerves Kémiai Intézet">SZKI</span>/Funkcionális Farmakológiai Csoport</span> ; <span class="author-name" mtid="10004542"><a href="/gui2/?type=authors&mode=browse&sel=10004542" target="_blank">Visy J (<span class="authorship-author-name">Benéné Visy Júlia</span> <span class="authorAux-mtmt"> Szerves kémia</span>) </a> </span> <span class="author-affil"><span title="MTA Természettudományi Kutatóközpont">MTA TTK</span>/Molekuláris Farmakológiai Intézet</span> ; <span class="author-name" mtid="10001101"><a href="/gui2/?type=authors&mode=browse&sel=10001101" target="_blank">Kardos J (<span class="authorship-author-name">Kardos Julianna</span> <span class="authorAux-mtmt"> Neurokémia, az idegi jelátvitel molekuláris mec...</span>) </a> </span> <span class="author-affil"><span title="MTA Természettudományi Kutatóközpont">MTA TTK</span>/Szerves Kémiai Intézet; <span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/<span title="Szerves Kémiai Intézet">SZKI</span>/Funkcionális Farmakológiai Csoport</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse¶ms=publication;2305501" target="_blank">Polyamidoamine dendrimer impairs mitochondrial oxidation in brain tissue</a></div> <div> <span class="journal-title">JOURNAL OF NANOBIOTECHNOLOGY</span> <span class="journal-issn">( <a target="_blank" href="https://portal.issn.org/resource/ISSN/1477-3155">1477-3155</a>)</span>: <span class="journal-volume">11</span> <span class="page"> Paper 9. 9 p. </span> <span class="year">(2013)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1186/1477-3155-11-9" target="_blank" href="https://doi.org/10.1186/1477-3155-11-9"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="5965" target="_blank" href="http://real.mtak.hu/5965"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000317644200001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000317644200001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84875688528" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84875688528"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="23556550" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23556550&dopt=Abstract"> PubMed </a> </span> </span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 28</span> | Független: 25 | Függő: 3 | Nem jelölt: 0 | WoS jelölt: 21 | Scopus jelölt: 22 | WoS/Scopus jelölt: 25 | DOI jelölt: 25 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;2305501&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 7 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 2305501</span> | <span class="status-data status-APPROVED"> Nyilvános </span> <span class="oldId">Régi azonosító: 2305501</span> | Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">Scopus</span> </div> <div class="lastModified">Utolsó módosítás: 2023.09.23. 11:04 MTMT API (MTMT API user, admin) </div> </div></div>