Flavonoid modulation of protein kinase C activation.
The flavonoid quercetin exhibited a biphasic effect on calcium and phospholipid-dependent protein kinase (protein kinase C) activity from rat brain and pig thyroid. At a low concentration (10(-7) M) quercetin stimulated the enzyme activity whereas at higher concentrations quercetin was inhibitory. By contrast the synthetic penta-0-ethylquercetin stimulated protein kinase C activity in a dose-dependent manner. When fresly dispersed pig thyroid cells were treated with penta-0-ethylquercetin or 12-0-tetradecanoylphorbol 13-acetate (TPA), a 50% decrease of the cytosolic protein kinase C activity was observed. These results suggest that the lipophilicity as well as other structural determinants may be crucial for the ability of flavonoids to regulate (inhibit or activate) the enzyme activity.
Picq
M
M
Laboratoire de Chimie Biologique, Institut National des Sciences Appliquées de lyon, Unité INSERM 205, Villeurbanne, France.
Dubois
M
M
Munari-Silem
Y
Y
Prigent
A F
AF
Pacheco
H
H
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000201:enzymology*
D004075:Diglycerides; D005419:Flavonoids; D010718:Phosphatidylserines; C057450:penta-O-ethylquercetin; D011794:Quercetin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C013965:diolein