Document Detail


Paeoniflorin, a potent natural compound, protects PC12 cells from MPP+ and acidic damage via autophagic pathway.
MedLine Citation:
PMID:  20558269     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (PF) is the principal bioactive component of Radix Paeoniae alba, which is widely used in Traditional Chinese Medicine for the treatment of neurodegenerative disorders such as Parkinson's disease (PD).
AIM OF THE STUDY: To evaluate the neuroprotective effects of PF on MPP(+)- or acid- (pH 5.0) induced injury in cultured PC12 cells and to investigate the activity of autophagy-lysosome pathway (ALP). Amiloride (Ami), a non-selective blocker of acid-sensing ion channels (ASICs), as a positive control drug, since it is neuroprotective in rodent models of PD.
MATERIALS AND METHODS: The cell viability was analyzed with MTT assay. The cell injury was assessed by lactate dehydrogenase (LDH) assay. Flow cytometry and Western blot analysis were used to study the apoptotic, calcium influx and autophagic mechanisms.
RESULTS: Ami (100 microM) and PF (50 microM) both protected PC12 cells against MPP(+)- or acid-induced injury as assessed by MTT assay, lactate dehydrogenase release, and apoptosis rate. The concentrations of cytosolic free Ca(2+) were raised after exposure to MPP(+) or acidosis, while Ami and PF both reduced the influx of Ca(2+). More importantly, we found that the mechanisms of neuroprotective effects of Ami and PF were closely associated with the upregulation of LC3-II protein, which is specifically associated with autophagic vacuole membranes. Furthermore, application of MPP(+) or acid induced the overexpression of LAMP2a, which is directly correlated with the activity of the chaperone-mediated autophagy pathway. However, Ami and PF inhibited the overexpression of LAMP2a.
CONCLUSIONS: Our data provide the first experimental evidence that PF modulates autophagy in models of neuron injury, as well as providing the first indication of a relationship between ASICs and ALP.
Authors:
Bi-Yin Cao; Ya-Ping Yang; Wei-Feng Luo; Cheng-Jie Mao; Rong Han; Xue Sun; Jing Cheng; Chun-Feng Liu
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-15
Journal Detail:
Title:  Journal of ethnopharmacology     Volume:  131     ISSN:  1872-7573     ISO Abbreviation:  J Ethnopharmacol     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7903310     Medline TA:  J Ethnopharmacol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  122-9     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
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