| Pisiferdiol and pisiferic acid isolated from Chamaecyparis pisifera activate protein phosphatase 2C in vitro and induce caspase-3/7-dependent apoptosis via dephosphorylation of Bad in HL60 cells. | |
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MedLine Citation:
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PMID: 20153620 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates and regulates apoptosis, stress response and growth-related pathways. In the course of screening for PP2C activators from natural sources, we isolated abietane-type diterpenes, pisiferdiol and pisiferic acid from Chamaecyparis pisifera. Pisiferdiol having a unique seven-membered ring showed more specific PP2C activation activity (1.3-fold at 100 microM) than pisiferic acid having a normal six-membered ring and oleic acid, which is known to activate PP2C. Pisiferdiol and pisiferic acid showed mixed-type activation with respect to alpha-casein, and this differed from the non-competitive activation of oleic acid in vitro. In vivo, the cytotoxicity of pisiferdiol toward human promyelocytic leukemia cell line HL60 with an IC(50) value of 18.3 microM was 2-fold and 7-fold stronger than those of pisiferic acid and oleic acid, and pisiferdiol induced apoptosis through a caspase 3/7-dependent mechanism involving the dephosphorylation of Bad(1), which is a PP2C substrate. We thus conclude that pisiferdiol and pisiferic acid are novel PP2C activators, and the more specific activator, pisiferdiol, may be a useful chemical probe to study PP2C-mediated signaling pathways, and a lead compound for pharmaceutical agents. |
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Authors:
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N Aburai; M Yoshida; M Ohnishi; K Kimura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-12 |
Journal Detail:
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Title: Phytomedicine : international journal of phytotherapy and phytopharmacology Volume: 17 ISSN: 1618-095X ISO Abbreviation: Phytomedicine Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-15 Completed Date: 2010-12-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9438794 Medline TA: Phytomedicine Country: Germany |
Other Details:
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Languages: eng Pagination: 782-8 Citation Subset: IM |
Copyright Information:
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2010 Elsevier GmbH. All rights reserved. |
Affiliation:
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Laboratory of Chemical Biology, The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Iwate 020-8550, Japan. |
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* Caspase 3 / metabolism* Caspase 7 / metabolism* Chamaecyparis / chemistry* Diterpenes / isolation & purification, pharmacology* Electrophoresis, Polyacrylamide Gel Enzyme Activation HL-60 Cells Humans Magnetic Resonance Spectroscopy Phosphoprotein Phosphatases / metabolism* Phosphorylation Spectrometry, Mass, Electrospray Ionization Spectrophotometry, Ultraviolet bcl-Associated Death Protein / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Diterpenes; 0/bcl-Associated Death Protein; 67494-15-9/pisiferic acid; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/protein phosphatase 2C; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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