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Article: Involvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2α in neuronal degeneration

TitleInvolvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2α in neuronal degeneration
Authors
Issue Date2002
Citation
Journal Of Neurochemistry, 2002, v. 83 n. 5, p. 1215-1225 How to Cite?
AbstractInhibition of protein translation plays an important role in apoptosis. While double-stranded RNA-dependent protein kinase (PKR) is named as it is activated by double-stranded RNA produced by virus, its activation induces an inhibition of protein translation and apoptosis via the phosphorylation of the eukaryotic initiation factor 2α (elF2cα). PKR is also a stress kinase and its levels increase during ageing. Here we show that PKR activation and elF2α phosphorylation play a significant role in apoptosis of neuroblastoma cells and primary neuronal cultures induced by the β-amyloid (Aβ) peptides, the calcium ionophore A23187 and flavonoids. The phosphorylation of elF2α and the number of apoptotic cells were enhanced in over-expressed wild-type PKR neuroblastoma cells exposed to Aβ peptide, while dominant-negative PKR reduced elF2α phosphorylation and apoptosis induced by Aβ peptide. Primary cultured neurons from PKR knockout mice were also less sensitive to Aβ peptide toxicity. Activation of PKR and elF2α pathway by Aβ peptide are triggered by an increase in intracellular calcium because the intracellular calcium chelator BAPTA-AM significantly reduced PKR phosphorylation. Taken together, these results reveal that PKR and elF2α phosphorylation could be involved in the molecular signalling events leading to neuronal apoptosis and death and could be a new target in neuroprotection.
Persistent Identifierhttp://hdl.handle.net/10722/149608
ISSN
2015 Impact Factor: 3.842
2015 SCImago Journal Rankings: 2.021
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChang, RCCen_US
dc.contributor.authorSuen, KCen_US
dc.contributor.authorMa, CHen_US
dc.contributor.authorElyaman, Wen_US
dc.contributor.authorNg, HKen_US
dc.contributor.authorHugon, Jen_US
dc.date.accessioned2012-06-26T05:55:55Z-
dc.date.available2012-06-26T05:55:55Z-
dc.date.issued2002en_US
dc.identifier.citationJournal Of Neurochemistry, 2002, v. 83 n. 5, p. 1215-1225en_US
dc.identifier.issn0022-3042en_US
dc.identifier.urihttp://hdl.handle.net/10722/149608-
dc.description.abstractInhibition of protein translation plays an important role in apoptosis. While double-stranded RNA-dependent protein kinase (PKR) is named as it is activated by double-stranded RNA produced by virus, its activation induces an inhibition of protein translation and apoptosis via the phosphorylation of the eukaryotic initiation factor 2α (elF2cα). PKR is also a stress kinase and its levels increase during ageing. Here we show that PKR activation and elF2α phosphorylation play a significant role in apoptosis of neuroblastoma cells and primary neuronal cultures induced by the β-amyloid (Aβ) peptides, the calcium ionophore A23187 and flavonoids. The phosphorylation of elF2α and the number of apoptotic cells were enhanced in over-expressed wild-type PKR neuroblastoma cells exposed to Aβ peptide, while dominant-negative PKR reduced elF2α phosphorylation and apoptosis induced by Aβ peptide. Primary cultured neurons from PKR knockout mice were also less sensitive to Aβ peptide toxicity. Activation of PKR and elF2α pathway by Aβ peptide are triggered by an increase in intracellular calcium because the intracellular calcium chelator BAPTA-AM significantly reduced PKR phosphorylation. Taken together, these results reveal that PKR and elF2α phosphorylation could be involved in the molecular signalling events leading to neuronal apoptosis and death and could be a new target in neuroprotection.en_US
dc.languageengen_US
dc.relation.ispartofJournal of Neurochemistryen_US
dc.subject.meshAmyloid Beta-Peptides - Toxicityen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCalcimycin - Toxicityen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshCell Counten_US
dc.subject.meshEukaryotic Initiation Factor-2 - Metabolismen_US
dc.subject.meshGenistein - Toxicityen_US
dc.subject.meshHumansen_US
dc.subject.meshIonophores - Toxicityen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshNeuroblastoma - Metabolism - Pathologyen_US
dc.subject.meshNeurons - Drug Effects - Metabolism - Pathologyen_US
dc.subject.meshPeptide Fragments - Toxicityen_US
dc.subject.meshPhosphorylation - Drug Effectsen_US
dc.subject.meshQuercetin - Toxicityen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshEif-2 Kinase - Metabolismen_US
dc.titleInvolvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2α in neuronal degenerationen_US
dc.typeArticleen_US
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_US
dc.identifier.authorityChang, RCC=rp00470en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1046/j.1471-4159.2002.01237.xen_US
dc.identifier.pmid12437593-
dc.identifier.scopuseid_2-s2.0-0036892618en_US
dc.identifier.hkuros75015-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036892618&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume83en_US
dc.identifier.issue5en_US
dc.identifier.spage1215en_US
dc.identifier.epage1225en_US
dc.identifier.isiWOS:000179571400021-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridChang, RCC=7403713410en_US
dc.identifier.scopusauthoridSuen, KC=7004577222en_US
dc.identifier.scopusauthoridMa, CH=35080792100en_US
dc.identifier.scopusauthoridElyaman, W=6603236614en_US
dc.identifier.scopusauthoridNg, HK=7401619354en_US
dc.identifier.scopusauthoridHugon, J=7103202992en_US

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