Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.cellsig.2005.12.006
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dc.titleU18666A-mediated apoptosis in cultured murine cortical neurons: Role of caspases, calpains and kinases
dc.contributor.authorKoh, C.H.V.
dc.contributor.authorDUAN WEI
dc.contributor.authorCheung, N.S.
dc.contributor.authorQi, R.Z.
dc.contributor.authorQu, D.
dc.contributor.authorMelendez, A.
dc.contributor.authorManikandan, J.
dc.contributor.authorBay, B.H.
dc.date.accessioned2011-07-25T02:42:51Z
dc.date.available2011-07-25T02:42:51Z
dc.date.issued2006
dc.identifier.citationKoh, C.H.V., DUAN WEI, Cheung, N.S., Qi, R.Z., Qu, D., Melendez, A., Manikandan, J., Bay, B.H. (2006). U18666A-mediated apoptosis in cultured murine cortical neurons: Role of caspases, calpains and kinases. Cellular Signalling 18 (10) : 1572-1583. ScholarBank@NUS Repository. https://doi.org/10.1016/j.cellsig.2005.12.006
dc.identifier.issn08986568
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/24321
dc.description.abstractStudies have suggested that cholesterol imbalance in the brain might be related to the development of neurological disorders such as Alzheimer's disease and Niemann-Pick disease type C. Previously, we have reported that U18666A, a cholesterol transport-inhibiting agent, leads to apoptosis and intracellular cholesterol accumulation in primary cortical neurons. In this study, we examined the effects of U18666A-mediated neuronal apoptosis, and found that chronic exposure to U18666A led to the activation of caspases and calpains and hyperphosphorylation of tau. Tau hyperphosphorylation is regulated by several kinases that phosphorylate specific sites of tau in vitro. Surprisingly, the kinase activity of cyclin-dependent kinase 5 decreased in U18666A-treated cortical neurons whereas its protein level remained unchanged. The amount of glycogen synthase kinase 3 and mitogen-activated protein kinases were found to decrease in their phosphorylated states by Western blot analysis. Gene transcription was further studied using microarray analysis. Genes encoding for kinases and phosphatases were differentially expressed with most up-regulated and some down-regulated in expression upon U18666A treatment. The activation of cysteine proteases and cholesterol accumulation with tauopathies may provide clues to the cellular mechanism of the inhibition of cholesterol transport-mediated cell death in neurodegenerative diseases. © 2005 Elsevier Inc. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.cellsig.2005.12.006
dc.sourceScopus
dc.subjectCalpain
dc.subjectCaspase
dc.subjectKinase
dc.subjectNeuronal apoptosis
dc.subjectTau
dc.subjectU18666A
dc.typeArticle
dc.contributor.departmentANATOMY
dc.contributor.departmentBIOCHEMISTRY
dc.contributor.departmentDIVISION OF ENVIRONMENTAL SCIENCE & ENGG
dc.contributor.departmentPHARMACOLOGY
dc.contributor.departmentPHYSIOLOGY
dc.description.doi10.1016/j.cellsig.2005.12.006
dc.description.sourcetitleCellular Signalling
dc.description.volume18
dc.description.issue10
dc.description.page1572-1583
dc.identifier.isiut000240391300004
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