Document Detail

Phorbol esters inhibit low density lipoprotein processing by cultured human fibroblasts.
MedLine Citation:
PMID:  3943605     Owner:  NLM     Status:  MEDLINE    
A 24 h pretreatment of MRC5 fibroblasts with the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) induced a marked decrease in low density lipoprotein (LDL) internalization and degradation; the maximal effect (about 55% decrease) was observed for 10(-7) M TPA. LDL binding was reduced about 35-40%. A significant decrease (about 25%) in LDL internalization was observed after a 2 h incubation of cells with the drug, but longer incubation times (4-6 h) led to a greater effect. Another tumor promoter, phorbol 12,13-dibutyrate decreased LDL internalization by about 35%, whereas the non-tumor promoting 4 alpha-phorbol 12,13-didecanoate had no effect. The protein kinase C inhibitor alpha-cobrotoxin partially antagonized the inhibitory effect of TPA on LDL internalization. The non-phorbol tumor promoter mezerein, another protein kinase C activator, decreased LDL uptake by about 50%. Finally, it was found that TPA had no significant effect on the affinity of the receptor for the LDL. These results suggest a role for protein kinase C in the LDL pathway in cultured human fibroblasts.
J C Mazière; C Mazière; L Mora; M Auclair; S Goldstein; J Polonovski
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  FEBS letters     Volume:  195     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  1986 Jan 
Date Detail:
Created Date:  1986-03-06     Completed Date:  1986-03-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  135-9     Citation Subset:  IM    
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MeSH Terms
Cell Line
Cobra Neurotoxin Proteins / pharmacology
Endocytosis / drug effects
Fibroblasts / metabolism
Lipoproteins, LDL / metabolism*
Phorbol Esters / pharmacology*
Receptors, LDL / drug effects,  metabolism
Terpenes / pharmacology
Reg. No./Substance:
0/Cobra Neurotoxin Proteins; 0/Diterpenes; 0/Lipoproteins, LDL; 0/Phorbol Esters; 0/Receptors, LDL; 0/Terpenes; 34807-41-5/mezerein

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