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- Publisher Website: 10.1021/acschemneuro.5b00115
- Scopus: eid_2-s2.0-84941917060
- PMID: 26147318
- WOS: WOS:000361505100007
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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
Title | 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 |
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Authors | |
Keywords | N-Propargyl caffeate amide (PACA) neuritogenic neuroprotection Nrf2/HO-1 Parkinson's disease |
Issue Date | 2015 |
Publisher | American 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? |
Abstract | Insufficient 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 Identifier | http://hdl.handle.net/10722/215633 |
ISSN | 2023 Impact Factor: 4.1 2023 SCImago Journal Rankings: 1.060 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yang, C | - |
dc.contributor.author | Zhao, J | - |
dc.contributor.author | Cheng, Y | - |
dc.contributor.author | Le, XC | - |
dc.contributor.author | Rong, J | - |
dc.date.accessioned | 2015-08-21T13:33:32Z | - |
dc.date.available | 2015-08-21T13:33:32Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | ACS Chemical Neuroscience , 2015 | - |
dc.identifier.issn | 1948-7193 | - |
dc.identifier.uri | http://hdl.handle.net/10722/215633 | - |
dc.description.abstract | Insufficient 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.language | eng | - |
dc.publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/page/acncdm/about.html | - |
dc.relation.ispartof | ACS Chemical Neuroscience | - |
dc.subject | N-Propargyl caffeate amide (PACA) | - |
dc.subject | neuritogenic | - |
dc.subject | neuroprotection | - |
dc.subject | Nrf2/HO-1 | - |
dc.subject | Parkinson's disease | - |
dc.title | 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 | - |
dc.type | Article | - |
dc.identifier.email | Rong, J: jrong@hku.hk | - |
dc.identifier.authority | Rong, J=rp00515 | - |
dc.identifier.doi | 10.1021/acschemneuro.5b00115 | - |
dc.identifier.pmid | 26147318 | - |
dc.identifier.scopus | eid_2-s2.0-84941917060 | - |
dc.identifier.hkuros | 246294 | - |
dc.identifier.hkuros | 247190 | - |
dc.identifier.isi | WOS:000361505100007 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 1948-7193 | - |