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Article: N-Propargyl Caffeate Amide (PACA) Potentiates Nerve Growth Factor (NGF)-Induced Neurite Outgrowth and Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Toxicity by Activating the Nrf2/HO-1 Pathway

TitleN-Propargyl Caffeate Amide (PACA) Potentiates Nerve Growth Factor (NGF)-Induced Neurite Outgrowth and Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Toxicity by Activating the Nrf2/HO-1 Pathway
Authors
Issue Date2015
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/page/acncdm/about.html
Citation
ACS Chemical Neuroscience , 2015 How to Cite?
AbstractInsufficient production of neurotrophic factors is implicated in the pathogenesis of various neurodegenerative disorders. The aim of the present study was to evaluate the potential of N-propargyl caffeate amide (PACA) to enhance nerve growth factor (NGF)-induced neurite outgrowth and the underlying mechanisms. We discovered that PACA not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine (6-OHDA) neurotoxicity in dopaminergic PC12 cells and primary rat midbrain neurons. To identify the PACA-binding proteins, we introduced a biotin tag to the covalent PACA-protein adducts via 'click chemistry' alkyne-azido cycloaddition. As a result, kelch-like ECH-associated protein 1 (Keap1) was isolated as the predominant protein from PACA treated PC12 cells. We demonstrated that the formation of PACA-Keap1 conjugates induced the nuclear translocation of transcription factor Nrf2 and the expression of antioxidant heme oxygenase-1 (HO-1). Importantly, specific HO-1 inhibitor SnPP diminished the neuroprotective and neuritogenic activities of PACA. Moreover, PACA attenuated 6-OHDA-induced production of neurotoxic reactive oxygen species and reactive nitrogen species. PACA also preserved mitochondrial membrane integrity and enhanced the cellular resistance against 6-OHDA neurotoxicity. These results suggest that PACA may exhibit neuroprotective and neuritogenic activities via activating the Nrf2/HO-1 antioxidant pathway.
Persistent Identifierhttp://hdl.handle.net/10722/215633
ISSN
2015 Impact Factor: 4.348
2015 SCImago Journal Rankings: 1.842

 

DC FieldValueLanguage
dc.contributor.authorYang, C-
dc.contributor.authorZhao, J-
dc.contributor.authorCheng, Y-
dc.contributor.authorLe, XC-
dc.contributor.authorRong, J-
dc.date.accessioned2015-08-21T13:33:32Z-
dc.date.available2015-08-21T13:33:32Z-
dc.date.issued2015-
dc.identifier.citationACS Chemical Neuroscience , 2015-
dc.identifier.issn1948-7193-
dc.identifier.urihttp://hdl.handle.net/10722/215633-
dc.description.abstractInsufficient production of neurotrophic factors is implicated in the pathogenesis of various neurodegenerative disorders. The aim of the present study was to evaluate the potential of N-propargyl caffeate amide (PACA) to enhance nerve growth factor (NGF)-induced neurite outgrowth and the underlying mechanisms. We discovered that PACA not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine (6-OHDA) neurotoxicity in dopaminergic PC12 cells and primary rat midbrain neurons. To identify the PACA-binding proteins, we introduced a biotin tag to the covalent PACA-protein adducts via 'click chemistry' alkyne-azido cycloaddition. As a result, kelch-like ECH-associated protein 1 (Keap1) was isolated as the predominant protein from PACA treated PC12 cells. We demonstrated that the formation of PACA-Keap1 conjugates induced the nuclear translocation of transcription factor Nrf2 and the expression of antioxidant heme oxygenase-1 (HO-1). Importantly, specific HO-1 inhibitor SnPP diminished the neuroprotective and neuritogenic activities of PACA. Moreover, PACA attenuated 6-OHDA-induced production of neurotoxic reactive oxygen species and reactive nitrogen species. PACA also preserved mitochondrial membrane integrity and enhanced the cellular resistance against 6-OHDA neurotoxicity. These results suggest that PACA may exhibit neuroprotective and neuritogenic activities via activating the Nrf2/HO-1 antioxidant pathway.-
dc.languageeng-
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/page/acncdm/about.html-
dc.relation.ispartofACS Chemical Neuroscience-
dc.titleN-Propargyl Caffeate Amide (PACA) Potentiates Nerve Growth Factor (NGF)-Induced Neurite Outgrowth and Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Toxicity by Activating the Nrf2/HO-1 Pathway-
dc.typeArticle-
dc.identifier.emailRong, J: jrong@hku.hk-
dc.identifier.authorityRong, J=rp00515-
dc.identifier.doi10.1021/acschemneuro.5b00115-
dc.identifier.pmid26147318-
dc.identifier.hkuros246294-
dc.identifier.hkuros247190-
dc.publisher.placeUnited States-

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