| pubmed-article:19427306 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C0006675 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C0763396 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C0030685 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C0680255 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C0391871 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C1283071 | lld:lifeskim |
| pubmed-article:19427306 | lifeskim:mentions | umls-concept:C1963578 | lld:lifeskim |
| pubmed-article:19427306 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:19427306 | pubmed:dateCreated | 2009-7-14 | lld:pubmed |
| pubmed-article:19427306 | pubmed:abstractText | Recent discoveries show that caspase-independent cell death pathways are a pervasive mechanism in neurodegenerative diseases, and apoptosis-inducing factor (AIF) is an important effector of this mode of neuronal death. There are currently two known mechanisms underlying AIF release following excitotoxic stress, PARP-1 and calpain. To test whether there is an interaction between PARP-1 and calpain in triggering AIF release, we used the NMDA toxicity model in rat primary cortical neurons. Exposure to NMDA resulted in AIF truncation and nuclear translocation, and shRNA-mediated knockdown of AIF resulted in neuroprotection. Both calpain and PARP-1 are involved with AIF processing as AIF truncation, nuclear translocation and neuronal death were attenuated by calpain inhibition using adeno-associated virus-mediated overexpression of the endogenous calpain inhibitor, calpastatin, or treatment with the PARP-1 inhibitor 3-ABA. Activation of PARP-1 is necessary for calpain activation as PARP-1 inhibition blocked mitochondrial calpain activation. Finally, NMDA toxicity induces mitochondrial Ca(2+) dysregulation in a PARP-1 dependent manner. Thus, PARP-1 and mitochondrial calpain activation are linked via PARP-1-induced alterations in mitochondrial Ca(2+) homeostasis. Collectively, these findings link the two seemingly independent mechanisms triggering AIF-induced neuronal death. | lld:pubmed |
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| pubmed-article:19427306 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19427306 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19427306 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19427306 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19427306 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19427306 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:19427306 | pubmed:issn | 1090-2430 | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:ChenJunJ | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:CaoGuodongG | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:KintnerDougla... | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:SunDandanD | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:SignoreArmand... | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:GaoYanqinY | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:VoslerPeter... | lld:pubmed |
| pubmed-article:19427306 | pubmed:author | pubmed-author:WangSupingS | lld:pubmed |
| pubmed-article:19427306 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19427306 | pubmed:volume | 218 | lld:pubmed |
| pubmed-article:19427306 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19427306 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19427306 | pubmed:pagination | 213-20 | lld:pubmed |
| pubmed-article:19427306 | pubmed:dateRevised | 2011-8-1 | lld:pubmed |
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