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Q111qc vSpeedyRINGO Inhibits Calpain-Directed Apoptosis in Neurons

Yildiz-Unal, Aysegul; Korulu, Sirin; Karabay, Arzu


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{
  "DOI": "10.3233/JAD-2012-120652", 
  "abstract": "The calcium-activated proteolytic enzyme calpain is one of the key proteins that can directly or indirectly drive neurons into apoptosis. The indirect way is through cyclin dependent kinase 5 (CDK5), a non-mitotic kinase, which is upregulated through calpain overactivation and followed by a subsequent increase in p53 and active caspase-3 levels under neurodegenerative conditions. The direct way is the upregulation of p53 by calpain itself, since p53 is a substrate for it. SpeedyRINGO is an atypical cell cycle regulator that has been shown to have protective effects in mitotic cells against apoptosis by inhibiting caspase-3 activation when p53 is present. Our aim was to reveal possible protective effects of SpeedyRINGO against calpain-induced caspase-3 activation in neurons which is crucial in terms of providing novel insights in preventing the caspase-3 activation cascade in neurodegeneration. For this reason, mRNA and protein levels were analyzed by qRT-PCR, western blotting, and immunofluorescence. We show that calpain overactivation leads to the upregulation of p53 and a subsequent increase in active caspase-3 level, indicating activation of apoptotic machinery in neurons. This calpain-directed caspase-3 activation upon upregulation of p53 is inhibited by the expression of SpeedyRINGO in rat hippocampal neurons. Therefore, SpeedyRINGO acts as a savior for neurons that are under apoptotisis due to caspase-3 activation.", 
  "author": [
    {
      "family": "Yildiz-Unal", 
      "given": " Aysegul"
    }, 
    {
      "family": "Korulu", 
      "given": " Sirin"
    }, 
    {
      "family": "Karabay", 
      "given": " Arzu"
    }
  ], 
  "container_title": "JOURNAL OF ALZHEIMERS DISEASE", 
  "id": "87281", 
  "issue": "4", 
  "issued": {
    "date-parts": [
      [
        2012, 
        1, 
        1
      ]
    ]
  }, 
  "page": "779-791", 
  "title": "Q111qc vSpeedyRINGO Inhibits Calpain-Directed Apoptosis in Neurons", 
  "type": "article-journal", 
  "volume": "31"
}
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