Document Detail

L-3-n-butyl-phthalide alleviates hydrogen peroxide-induced apoptosis by PKC pathway in human neuroblastoma SK-N-SH cells.
MedLine Citation:
PMID:  21063685     Owner:  NLM     Status:  MEDLINE    
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.
Ying Peng; Yanli Hu; Nan Feng; Ling Wang; Xiaoliang Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-10
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  383     ISSN:  1432-1912     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-05     Completed Date:  2011-07-15     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  91-9     Citation Subset:  IM    
Pharmacology Department, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1, Xiannongtan Street, Beijing 100050, China.
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MeSH Terms
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / genetics
Benzofurans / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
Gene Expression / drug effects,  genetics
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
Reg. No./Substance:
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 protein, human; EC protein, human; EC Kinase C; EC Kinase C-alpha; EC Kinase C-epsilon

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