Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis
Identifieur interne : 001811 ( Ncbi/Checkpoint ); précédent : 001810; suivant : 001812Poly(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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PMC:4104885Le document en format XML
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, Baltimore,<addr-line>MD</addr-line>
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<author><name sortKey="Karuppagounder, Senthilkumar S" sort="Karuppagounder, Senthilkumar S" uniqKey="Karuppagounder S" first="Senthilkumar S." last="Karuppagounder">Senthilkumar S. Karuppagounder</name>
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<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>
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<wicri:noCountry code="subfield">Institute for Cell Engineering</wicri:noCountry>
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<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>
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<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>
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<affiliations><list><country><li>Canada</li>
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<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>
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