Document Detail

The effect of plant phenols on the expression and activity of phorbol ester-induced PKC in mouse epidermis.
MedLine Citation:
PMID:  17196728     Owner:  NLM     Status:  MEDLINE    
Protein kinase C (PKC) is thought to be a major intracellular receptor for the mouse skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The diversity of PKC isoforms, and their central role in many signaling pathways, makes them important targets for potential chemopreventive agents. Our earlier studies showed that the plant phenols protocatechuic acid, chlorogenic acid and tannic acid alter the activity of enzymes involved in carcinogen activation, inhibit the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in mouse epidermis and decrease the level of lipid peroxidation in the epidermal microsomes. In the present study the effects of protocatechuic acid, chlorogenic acid and tannic acid on TPA-stimulated PKC isozymes alpha, beta(1), beta(2), gamma and zeta activity, and their distribution in mouse epidermis, was examined. The application of these phenolics 15 min before a single dose (3.4 nmol) of TPA resulted in significant inhibition of PKC translocation and a subsequent decrease in classical and novel/atypical PKC isoforms in comparison to a group of mice treated with TPA alone. The most potent inhibitor of PKC translocation and activity was tannic acid. This compound increased the levels of PKCalpha, beta(1), beta(2) in the cytosolic fraction by between 127% and 492% in comparison with TPA treated group of mice. Tannic acid decreased the activities of all three PKC classes by approximately 94% in the membrane fraction in comparison with the TPA treated group of animals. The effect of protocatechuic and chlorogenic acids on the distribution and activity of PKC isozymes was moderate. These compounds mostly affected translocation of PKCalpha and subsequently the activity of classical PKC. The enzyme activity in the particulate fraction was reduced by 59% and 43% in comparison with the TPA group, respectively. Thus, the results of these studies suggest that the subcellular distribution of PKC isoforms, and the activity of PKCs, can be modulated by plant phenolic acids, particularly tannic acid, and that such actions represent a part of the anti-promotional activity of these substances in mouse epidermis.
Hanna Szaefer; Jolanta Kaczmarek; Maria Rybczyńska; Wanda Baer-Dubowska
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-06
Journal Detail:
Title:  Toxicology     Volume:  230     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-15     Completed Date:  2007-03-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  1-10     Citation Subset:  IM    
Department of Pharmaceutical Biochemistry, Poznań University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
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MeSH Terms
Anticarcinogenic Agents / pharmacology
Blotting, Western
Chlorogenic Acid / pharmacology
Cytosol / drug effects,  enzymology
Enzyme Induction / drug effects
Epidermis / drug effects,  enzymology*
Hydroxybenzoic Acids / pharmacology
Isoenzymes / biosynthesis,  metabolism
Phenols / pharmacology*
Phorbol Esters / pharmacology*
Plants / chemistry*
Protein Kinase C / biosynthesis*,  metabolism*
Subcellular Fractions / drug effects,  enzymology
Tannins / pharmacology
Tetradecanoylphorbol Acetate / pharmacology
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Hydroxybenzoic Acids; 0/Isoenzymes; 0/Phenols; 0/Phorbol Esters; 0/Tannins; 16561-29-8/Tetradecanoylphorbol Acetate; 327-97-9/Chlorogenic Acid; 99-50-3/protocatechuic acid; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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