| L-3-n-butyl-phthalide alleviates hydrogen peroxide-induced apoptosis by PKC pathway in human neuroblastoma SK-N-SH cells. | |
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MedLine Citation:
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PMID: 21063685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alzheimer's disease (AD) is the most common form of dementia. Oxidative stress is one of the earliest events in the neurological and pathological changes of AD. L-3-n-butyl-phthalide (L-NBP), an anti-cerebral ischemia agent, has been shown a potential in AD treatment. In this study, we investigated the neuroprotective effect of L-NBP on hydrogen peroxide (H₂O₂)-induced apoptosis in human neuroblastoma SK-N-SH cells. H₂O₂ significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that H₂O₂ induced neurotoxicity. In addition, real-time PCR and western blot studies showed that Bcl-2 and Bcl-w expressions were decreased, and Bax expression was increased with H₂O₂ treatment. Moreover, protein kinase C (PKC) α expression was down-regulated after H₂O₂ treatment. All of these phenotypes induced by H₂O₂ were markedly reversed by L-NBP. Pretreatment with L-NBP significantly increased cell viability of H₂O₂-damaged cells, and reduced H₂O₂-induced neuronal apoptosis. L-NBP treatment at dose of 10 μM inhibited H₂O₂-induced down-regulation of Bcl-2, Bcl-w, and PKCα but also attenuated the overexpression of Bax. PKC inhibitor, calphostin C, significantly attenuated the protective effects of L-NBP. Our findings suggest that L-NBP may protect neurons against H₂O₂-induced apoptosis by modulating apoptosis-related genes and activating PKCα pathway. |
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Authors:
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Ying Peng; Yanli Hu; Nan Feng; Ling Wang; Xiaoliang Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-10 |
Journal Detail:
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Title: Naunyn-Schmiedeberg's archives of pharmacology Volume: 383 ISSN: 1432-1912 ISO Abbreviation: Naunyn Schmiedebergs Arch. Pharmacol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-05 Completed Date: 2011-07-15 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 0326264 Medline TA: Naunyn Schmiedebergs Arch Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 91-9 Citation Subset: IM |
Affiliation:
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Pharmacology Department, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1, Xiannongtan Street, Beijing 100050, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Apoptosis Regulatory Proteins / genetics Benzofurans / pharmacology* Cell Line, Tumor Cell Survival / drug effects Gene Expression / drug effects, genetics Humans Hydrogen Peroxide / pharmacology* Naphthalenes / pharmacology Neuroblastoma / metabolism* Neuroprotective Agents / pharmacology Protein Kinase C / antagonists & inhibitors, metabolism* Protein Kinase C-alpha / antagonists & inhibitors, metabolism Protein Kinase C-epsilon / antagonists & inhibitors, metabolism Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-bcl-2 / metabolism Signal Transduction / drug effects*, physiology bcl-2-Associated X Protein / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/BAX protein, human; 0/BCL2L2 protein, human; 0/Benzofurans; 0/Naphthalenes; 0/Neuroprotective Agents; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 121263-19-2/calphostin C; 6066-49-5/3-n-butylphthalide; 7722-84-1/Hydrogen Peroxide; EC 2.7.1.-/protein kinase C gamma; EC 2.7.11.13/PRKCA protein, human; EC 2.7.11.13/PRKCE protein, human; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/Protein Kinase C-alpha; EC 2.7.11.13/Protein Kinase C-epsilon |
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