Evidence for the Involvement of Par-4 in Ischemic Neuron Cell Death

DOI Web Site Web Site 被引用文献2件
  • Carsten Culmsee
    Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, U.S.A.
  • Yuan Zhu
    Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Marburg, Germany
  • Josef Krieglstein
    Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Marburg, Germany
  • Mark P. Mattson
    Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, U.S.A.

抄録

<jats:p> After a stroke many neurons in the ischemic brain tissue die by a process called apoptosis, a form of cell death that may be preventable. The specific molecular cascades that mediate ischemic neuronal death are not well understood. The authors recently identified prostate apoptosis response-4 (Par-4) as a protein that participates in the death of cultured hippocampal neurons induced by trophic factor withdrawal and exposure to glutamate. Here, the authors show that Par-4 levels increase in vulnerable populations of hippocampal and striatal neurons in rats after transient forebrain ischemia; Par-4 levels increased within 6 hours of reperfusion and remained elevated in neurons undergoing apoptosis 3 days later. After transient focal ischemia in mice, Par-4 levels were increased 6 to12 hours after reperfusion in the infarcted cortex and the striatum, and activation of caspase-8 occurred with a similar time course. Par-4 immunoreactivity was localized predominantly in cortical neurons at the border of the infarct area. A Par-4 antisense oligonucleotide protected cultured hippocampal neurons against apoptosis induced by chemical hypoxia and significantly reduced focal ischemic damage in mice. The current data suggest that early up-regulation of Par-4 plays a pivotal role in ischemic neuronal death in animal models of stroke and cardiac arrest. </jats:p>

収録刊行物

被引用文献 (2)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ