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Article: Modulation of calcium/calmodulin kinase-II provides partial neuroprotection against beta-amyloid peptide toxicity

TitleModulation of calcium/calmodulin kinase-II provides partial neuroprotection against beta-amyloid peptide toxicity
Authors
Issue Date2004
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJN
Citation
European Journal Of Neuroscience, 2004, v. 19 n. 8, p. 2047-2055 How to Cite?
AbstractBeta-amyloid (Aβ) peptide-induced neurotoxicity has been implicated in the pathogenesls of Alzheimer's disease (AD). The exact mechanism by which Aβ peptides trigger neuronal death is not well defined and may be related to an abrupt increase in intracellular calcium, leading to the activation of many pro-apoptotic pathways. While modulation of intracellular calcium increase receives much attention for pharmaceutical intervention, Ca2+- mediated pro-apoptotic signalling pathways have not been systematically studied. We have reported our study on the roles of calcium/calmodulin-dependent protein kinase II (CaMKII) in Aβ peptide neurotoxicity. By treating the primary cortical neurons exposed to Aβ peptides (Aβ25-35 and Aβ1-42) with two selective CaMKII inhibitors, autocamtide-related inhibitory peptide (AIP) and KN93, Aβ peptide neurotoxicity was significantly reduced. Release of LDH and DNA fragmentation/ condensation (by DAPI staining) in neurons exposed to Aβ peptides were significantly decreased in the presence of AIP and KN93. While these inhibitors significantly attenuated Aβ peptide-triggered activation of caspase-2 and caspase-3, and AIP significantly decreased the degree of tau phosphorylation of the Aβ peptide-treated neurons at early time, they could elicit partial neuroprotection only. Pharmacological inhibitor targeting calmodulin, W7, did not provide neuroprotection. Morphine, which activates CaMKII via μ receptors, augments Aβ-induced LDH release, caspase-2 and caspase-3 activities and neuronal apoptosis. Taken together, although CaMKII plays a role in Aβ peptide neurotoxicity, pharmacological inhibition cannot afford complete neuroprotection.
Persistent Identifierhttp://hdl.handle.net/10722/67890
ISSN
2015 Impact Factor: 2.975
2015 SCImago Journal Rankings: 2.130
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLin, KFen_HK
dc.contributor.authorChang, RCCen_HK
dc.contributor.authorSuen, KCen_HK
dc.contributor.authorSo, KFen_HK
dc.contributor.authorHugon, Jen_HK
dc.date.accessioned2010-09-06T05:59:12Z-
dc.date.available2010-09-06T05:59:12Z-
dc.date.issued2004en_HK
dc.identifier.citationEuropean Journal Of Neuroscience, 2004, v. 19 n. 8, p. 2047-2055en_HK
dc.identifier.issn0953-816Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/67890-
dc.description.abstractBeta-amyloid (Aβ) peptide-induced neurotoxicity has been implicated in the pathogenesls of Alzheimer's disease (AD). The exact mechanism by which Aβ peptides trigger neuronal death is not well defined and may be related to an abrupt increase in intracellular calcium, leading to the activation of many pro-apoptotic pathways. While modulation of intracellular calcium increase receives much attention for pharmaceutical intervention, Ca2+- mediated pro-apoptotic signalling pathways have not been systematically studied. We have reported our study on the roles of calcium/calmodulin-dependent protein kinase II (CaMKII) in Aβ peptide neurotoxicity. By treating the primary cortical neurons exposed to Aβ peptides (Aβ25-35 and Aβ1-42) with two selective CaMKII inhibitors, autocamtide-related inhibitory peptide (AIP) and KN93, Aβ peptide neurotoxicity was significantly reduced. Release of LDH and DNA fragmentation/ condensation (by DAPI staining) in neurons exposed to Aβ peptides were significantly decreased in the presence of AIP and KN93. While these inhibitors significantly attenuated Aβ peptide-triggered activation of caspase-2 and caspase-3, and AIP significantly decreased the degree of tau phosphorylation of the Aβ peptide-treated neurons at early time, they could elicit partial neuroprotection only. Pharmacological inhibitor targeting calmodulin, W7, did not provide neuroprotection. Morphine, which activates CaMKII via μ receptors, augments Aβ-induced LDH release, caspase-2 and caspase-3 activities and neuronal apoptosis. Taken together, although CaMKII plays a role in Aβ peptide neurotoxicity, pharmacological inhibition cannot afford complete neuroprotection.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJNen_HK
dc.relation.ispartofEuropean Journal of Neuroscienceen_HK
dc.rightsEuropean Journal of Neuroscience. Copyright © Blackwell Publishing Ltd.en_HK
dc.subject.meshAmyloid beta-Peptides - toxicityen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCalcium-Calmodulin-Dependent Protein Kinase Type 2en_HK
dc.subject.meshCalcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors - metabolismen_HK
dc.subject.meshCaspases - metabolismen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshEnzyme Activation - drug effects - physiologyen_HK
dc.subject.meshEnzyme Inhibitors - pharmacologyen_HK
dc.subject.meshNeurons - drug effects - enzymologyen_HK
dc.subject.meshNeuroprotective Agents - antagonists & inhibitors - metabolismen_HK
dc.subject.meshPeptide Fragments - toxicityen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Sprague-Dawleyen_HK
dc.titleModulation of calcium/calmodulin kinase-II provides partial neuroprotection against beta-amyloid peptide toxicityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0953-816X&volume=19&spage=2047&epage=2055&date=2004&atitle=Modulation+of+calcium/calmodulin+kinase-II+provides+partial+neuroprotection+against+beta-amyloid+peptide+toxicityen_HK
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_HK
dc.identifier.emailSo, KF:hrmaskf@hkucc.hku.hken_HK
dc.identifier.authorityChang, RCC=rp00470en_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.0953-816X.2004.03245.xen_HK
dc.identifier.pmid15090032-
dc.identifier.scopuseid_2-s2.0-2342468029en_HK
dc.identifier.hkuros85958en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2342468029&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue8en_HK
dc.identifier.spage2047en_HK
dc.identifier.epage2055en_HK
dc.identifier.isiWOS:000221197600005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLin, KF=8744549500en_HK
dc.identifier.scopusauthoridChang, RCC=7403713410en_HK
dc.identifier.scopusauthoridSuen, KC=7004577222en_HK
dc.identifier.scopusauthoridSo, KF=34668391300en_HK
dc.identifier.scopusauthoridHugon, J=7103202992en_HK

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