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Conference Paper: The mood stabilizer agents, lithium and valproate, inhibit staurosporine-induced apoptosis and eukaryotic initiation factor-2 alpha phosphorylation in SH-SY5Y neuroblastoma cells

TitleThe mood stabilizer agents, lithium and valproate, inhibit staurosporine-induced apoptosis and eukaryotic initiation factor-2 alpha phosphorylation in SH-SY5Y neuroblastoma cells
Authors
KeywordsPROTEIN TRANSLATION
CELL DEATH
CELL CULTURE
NEUROPROTECTION
Issue Date2001
PublisherSociety for Neuroscience
Citation
Neuroscience 2001, San Diego, CA, 10-15 November 2001, Presentation Number: 772.18 How to Cite?
AbstractBoth lithium and valproate have been used for the treatment of bipolar (manic-depressive) disorders. Despite their efficacy, the molecular mechanisms underlying their action remained to be elucidated. Eukaryotic initiation factor2a (eIF2a) plays a key role in protein translation and elongation. The phosphorylation of eIF2a involves several protein kinases and negatively regulates its activity and promotes apoptosis. This study aims to examine whether reduction of eIF2a phosphorylation exerts beneficial effects to neurons against stress. In this study, human neuroblastoma SH-SY5Y cell culture was exposed to staurosporine to induce apoptosis and cell death as shown by cell shrinkage, nuclei condensation or fragmentation and lactate dehydrogenase (LDH) release. Immunoblot techniques showed that apoptosis was associated with an increase in the phosphorylation of eIF2a on the serine-51 epitope in a time- and dose-dependent manner. Furthermore, neuroblastoma cells pretreated with either lithium chloride (LiCl) or sodium valproate (VPA) per se did not elicit morphological changes of apoptosis. Both mood stabilizers provided protection for neurons by reducing staurosporine-induced apoptosis as well as the increase in eIF2a phosphorylation. Our results suggest that a novel mode of neuroprotection is mediated by lithium and valproate which may explain some of the long-term therapeutic effects of mood stabilizing agents.
Persistent Identifierhttp://hdl.handle.net/10722/95698

 

DC FieldValueLanguage
dc.contributor.authorElyaman, Wen_HK
dc.contributor.authorChang, RCCen_HK
dc.contributor.authorHugon, Jen_HK
dc.date.accessioned2010-09-25T16:10:26Z-
dc.date.available2010-09-25T16:10:26Z-
dc.date.issued2001en_HK
dc.identifier.citationNeuroscience 2001, San Diego, CA, 10-15 November 2001, Presentation Number: 772.18en_HK
dc.identifier.urihttp://hdl.handle.net/10722/95698-
dc.description.abstractBoth lithium and valproate have been used for the treatment of bipolar (manic-depressive) disorders. Despite their efficacy, the molecular mechanisms underlying their action remained to be elucidated. Eukaryotic initiation factor2a (eIF2a) plays a key role in protein translation and elongation. The phosphorylation of eIF2a involves several protein kinases and negatively regulates its activity and promotes apoptosis. This study aims to examine whether reduction of eIF2a phosphorylation exerts beneficial effects to neurons against stress. In this study, human neuroblastoma SH-SY5Y cell culture was exposed to staurosporine to induce apoptosis and cell death as shown by cell shrinkage, nuclei condensation or fragmentation and lactate dehydrogenase (LDH) release. Immunoblot techniques showed that apoptosis was associated with an increase in the phosphorylation of eIF2a on the serine-51 epitope in a time- and dose-dependent manner. Furthermore, neuroblastoma cells pretreated with either lithium chloride (LiCl) or sodium valproate (VPA) per se did not elicit morphological changes of apoptosis. Both mood stabilizers provided protection for neurons by reducing staurosporine-induced apoptosis as well as the increase in eIF2a phosphorylation. Our results suggest that a novel mode of neuroprotection is mediated by lithium and valproate which may explain some of the long-term therapeutic effects of mood stabilizing agents.-
dc.languageengen_HK
dc.publisherSociety for Neuroscience-
dc.relation.ispartofSociety for Neuroscience Annual Meetingen_HK
dc.subjectPROTEIN TRANSLATION-
dc.subjectCELL DEATH-
dc.subjectCELL CULTURE-
dc.subjectNEUROPROTECTION-
dc.titleThe mood stabilizer agents, lithium and valproate, inhibit staurosporine-induced apoptosis and eukaryotic initiation factor-2 alpha phosphorylation in SH-SY5Y neuroblastoma cellsen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChang, RCC: rccchang@hkucc.hku.hken_HK
dc.identifier.emailHugon, J: jhugon@hkucc.hku.hken_HK
dc.identifier.authorityChang, RCC=rp00470en_HK
dc.identifier.hkuros64069en_HK

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