Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis
Identifieur interne : 000969 ( Main/Exploration ); précédent : 000968; suivant : 000970Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis
Auteurs : Shaida A. Andrabi ; George K. E. Umanah ; Calvin Chang ; Daniel A. Stevens ; Senthilkumar S. Karuppagounder ; Jean-Philippe Gagné [Canada] ; Guy G. Poirier [Canada] ; Valina L. Dawson ; Ted M. DawsonSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Abstract
Excessive activation of poly(ADP-ribose) (PAR) polymerase (PARP) is intimately linked to cell death in a variety of organ systems. It has long been thought that the cell death caused by excessive activation of PARP occurs through the catalytic consumption of NAD+ followed by reduction of ATP and bioenergetic collapse. This study shows that the bioenergetic collapse is caused not by the consumption of NAD+ but by PAR-dependent inhibition of hexokinase activity leading to defects in glycolysis. These results are consistent with the notion that cell death induced by excessive PARP activity (parthanatos) is an active cell-death program that is initiated by PAR signaling.
Url:
DOI: 10.1073/pnas.1405158111
PubMed: 24987120
PubMed Central: 4104885
Affiliations:
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Andrabi</name><affiliation><nlm:aff id="aff1">Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,</nlm:aff><wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Umanah, George K E" sort="Umanah, George K E" uniqKey="Umanah G" first="George K. E." last="Umanah">George K. E. Umanah</name><affiliation><nlm:aff id="aff1">Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,</nlm:aff><wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Chang, Calvin" sort="Chang, Calvin" uniqKey="Chang C" first="Calvin" last="Chang">Calvin Chang</name><affiliation><nlm:aff id="aff1">Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,</nlm:aff><wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Biomedical Engineering,</nlm:aff></affiliation></author><author><name sortKey="Stevens, Daniel A" sort="Stevens, Daniel A" uniqKey="Stevens D" first="Daniel A." last="Stevens">Daniel A. Stevens</name><affiliation><nlm:aff id="aff1">Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,</nlm:aff><wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff7">Solomon H. Snyder Department of Neuroscience,<institution>The Johns Hopkins University School of Medicine</institution>, Baltimore,<addr-line>MD</addr-line> 21205</nlm:aff></affiliation></author><author><name sortKey="Karuppagounder, Senthilkumar S" sort="Karuppagounder, Senthilkumar S" uniqKey="Karuppagounder S" first="Senthilkumar S." last="Karuppagounder">Senthilkumar S. Karuppagounder</name><affiliation><nlm:aff id="aff1">Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,</nlm:aff><wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Gagne, Jean Philippe" sort="Gagne, Jean Philippe" uniqKey="Gagne J" first="Jean-Philippe" last="Gagné">Jean-Philippe Gagné</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Centre de Recherche du CHU de Québec, Université Laval, Québec</institution>,<country>Canada</country> G1V 4G2</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Poirier, Guy G" sort="Poirier, Guy G" uniqKey="Poirier G" first="Guy G." last="Poirier">Guy G. Poirier</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Centre de Recherche du CHU de Québec, Université Laval, Québec</institution>,<country>Canada</country> G1V 4G2</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dawson, Valina L" sort="Dawson, Valina L" uniqKey="Dawson V" first="Valina L." last="Dawson">Valina L. Dawson</name><affiliation><nlm:aff id="aff1">Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,</nlm:aff><wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff7">Solomon H. Snyder Department of Neuroscience,<institution>The Johns Hopkins University School of Medicine</institution>, Baltimore,<addr-line>MD</addr-line> 21205</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff4">Physiology</nlm:aff></affiliation></author><author><name sortKey="Dawson, Ted M" sort="Dawson, Ted M" uniqKey="Dawson T" first="Ted M." last="Dawson">Ted M. Dawson</name><affiliation><nlm:aff id="aff1">Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,</nlm:aff><wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff7">Solomon H. Snyder Department of Neuroscience,<institution>The Johns Hopkins University School of Medicine</institution>, Baltimore,<addr-line>MD</addr-line> 21205</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff5">Pharmacology and Molecular Sciences</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Excessive activation of poly(ADP-ribose) (PAR) polymerase (PARP) is intimately linked to cell death in a variety of organ systems. It has long been thought that the cell death caused by excessive activation of PARP occurs through the catalytic consumption of NAD<sup>+</sup> followed by reduction of ATP and bioenergetic collapse. This study shows that the bioenergetic collapse is caused not by the consumption of NAD<sup>+</sup> but by PAR-dependent inhibition of hexokinase activity leading to defects in glycolysis. These results are consistent with the notion that cell death induced by excessive PARP activity (parthanatos) is an active cell-death program that is initiated by PAR signaling.</p></div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Andrabi, Shaida A" sort="Andrabi, Shaida A" uniqKey="Andrabi S" first="Shaida A." last="Andrabi">Shaida A. Andrabi</name><name sortKey="Chang, Calvin" sort="Chang, Calvin" uniqKey="Chang C" first="Calvin" last="Chang">Calvin Chang</name><name sortKey="Dawson, Ted M" sort="Dawson, Ted M" uniqKey="Dawson T" first="Ted M." last="Dawson">Ted M. Dawson</name><name sortKey="Dawson, Valina L" sort="Dawson, Valina L" uniqKey="Dawson V" first="Valina L." last="Dawson">Valina L. Dawson</name><name sortKey="Karuppagounder, Senthilkumar S" sort="Karuppagounder, Senthilkumar S" uniqKey="Karuppagounder S" first="Senthilkumar S." last="Karuppagounder">Senthilkumar S. Karuppagounder</name><name sortKey="Stevens, Daniel A" sort="Stevens, Daniel A" uniqKey="Stevens D" first="Daniel A." last="Stevens">Daniel A. Stevens</name><name sortKey="Umanah, George K E" sort="Umanah, George K E" uniqKey="Umanah G" first="George K. E." last="Umanah">George K. E. Umanah</name></noCountry><country name="Canada"><noRegion><name sortKey="Gagne, Jean Philippe" sort="Gagne, Jean Philippe" uniqKey="Gagne J" first="Jean-Philippe" last="Gagné">Jean-Philippe Gagné</name></noRegion><name sortKey="Poirier, Guy G" sort="Poirier, Guy G" uniqKey="Poirier G" first="Guy G." last="Poirier">Guy G. Poirier</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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