| Protective effect of (-)clausenamide against Abeta-induced neurotoxicity in differentiated PC12 cells. | |
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MedLine Citation:
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PMID: 20674676 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The neurotoxicity of aggregated beta-amyloid (Abeta) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). In the present study, we investigated the effect of (-)clausenamide ((-)Clau), an aqueous extract of leaves of Clausena lassium (lour) skeel, on the neurotoxicity of Abeta(25-35). The viability of differentiated PC12 cells was determined by MTT assay. Apoptosis was detected by flow cytometry. DCFH-DA was used for assessment of intracellular ROS generation, JC-1 and Rhodamine 123 for measurement of mitochondrial transmembrane potential (MMP). The intracellular calcium was determined with Fluo-3. The phosphorylation of p38 MAPK and the expression of Bcl-2, Bax, P53, Caspase 3 were examined by Western blot. The results showed that (-)Clau significantly elevated cell viability. Furthermore, (-)Clau arrested the apoptotic cascade by reversing overload of calcium, preventing ROS generation, moderated the dissipation of MMP and the misbalance of Bcl-2 and Bax, inhibiting the activation of p38 MAPK and the expression of P53 and cleaved Caspase 3. Our results suggested that (-)Clau may be a therapeutic agent for AD. |
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Authors:
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Jin-Feng Hu; Shi-Feng Chu; Na Ning; Yu-He Yuan; Wei Xue; Nai-Hong Chen; Jun-Tian Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-30 |
Journal Detail:
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Title: Neuroscience letters Volume: 483 ISSN: 1872-7972 ISO Abbreviation: Neurosci. Lett. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-08-30 Completed Date: 2010-12-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600130 Medline TA: Neurosci Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 78-82 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Key Laboratory of Bioactive Substances and Resources Utilization, Ministry of Education, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan street, Xuanwu district, Beijing 100050, China. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid beta-Peptides
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pharmacology* Analysis of Variance Animals Apoptosis / drug effects* Blotting, Western Calcium / metabolism Caspase 3 / metabolism Cell Differentiation Lactams / pharmacology* Lignans / pharmacology* PC12 Cells Phosphorylation / drug effects Proto-Oncogene Proteins c-bcl-2 / metabolism Rats Signal Transduction / drug effects Tumor Suppressor Protein p53 / metabolism bcl-2-Associated X Protein / metabolism p38 Mitogen-Activated Protein Kinases / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/Lactams; 0/Lignans; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 103541-15-7/clausenamide; 7440-70-2/Calcium; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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