Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/38570
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dc.contributor.authorLin, Hsiao-Yunen_US
dc.contributor.authorYeh, Wei-Lanen_US
dc.contributor.authorHuang, Bor-Renen_US
dc.contributor.authorLin, Chingjuen_US
dc.contributor.authorLai, Chih-Hoen_US
dc.contributor.authorLin, Hoen_US
dc.contributor.authorLu, Dah-Yuuen_US
dc.date2012-11zh_TW
dc.date.accessioned2014-06-06T08:00:56Z-
dc.date.available2014-06-06T08:00:56Z-
dc.identifier.urihttp://hdl.handle.net/11455/38570-
dc.description.abstractBackground: Desipramine is known principally as a tricyclic antidepressant drug used to promote recovery of depressed patients. It has also been used in a number of other psychiatric and medical conditions. The present study is the first to investigate the neuroprotective effect of desipramine. Methodology/Principal Findings: Mes23.5 dopaminergic cells were used to examine neuroprotective effect of desipramine. Western blot, reverse transcription-PCR, MTT assay, siRNA transfection and electrophoretic mobility shift assay (EMSA) were carried out to assess the effects of desipramine. Desipramine induces endogenous anti-oxidative enzyme, heme oxygenase- 1 (HO-1) protein and mRNA expression in concentration- and time-dependent manners. A different type of antidepressant SSRI (selective serotonin reuptake inhibitor), fluoxetine also shows similar effects of desipramine on HO-1 expression. Moreover, desipramine induces HO-1 expression through activation of ERK and JNK signaling pathways. Desipramine also increases NF-E2-related factor-2 (Nrf2) accumulation in the nucleus and enhances Nrf2-DNA binding activity. Moreover, desipramine-mediated increase of HO-1 expression is reduced by transfection with siRNA against Nrf2. On the other hand, pretreatment of desipramine protects neuronal cells against rotenone- and 6-hydroxydopamine (6-OHDA)-induced neuronal death. Furthermore, inhibition of HO-1 activity by a HO-1 pharmacological inhibitor, ZnPP IX, attenuates the neuroprotective effect of desipramine. Otherwise, activation of HO-1 activity by HO-1 activator and inducer protect 6- OHDA-induced neuronal death. Conclusions/Significance: These findings suggest that desipramine-increased HO-1 expression is mediated by Nrf2 activation through the ERK and JNK signaling pathways. Our results also suggest that desipramine provides a novel effect of neuroprotection, and neurodegenerative process might play an important role in depression disorder.en_US
dc.language.isoen_USzh_TW
dc.relationPLoS ONE, Volume 7, Issue 11en_US
dc.relation.urihttp://dx.doi.org/10.1371/journal.pone.0050138en_US
dc.titleDesipramine Protects Neuronal Cell Death and Induces Heme Oxygenase-1 Expression in Mes23.5 Dopaminergic Neuronsen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1371/journal.pone.0050138zh_TW
dc.contributor.catalogerWei Chun Wangen_US
item.grantfulltextnone-
item.openairetypeJournal Article-
item.languageiso639-1en_US-
item.fulltextno fulltext-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
Appears in Collections:生命科學系所
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