Flavonoids differentially inhibit guinea pig epidermal cytosolic phospholipase A2.
Cytosolic phospholipase A2 (cPLA2) is believed to involve the regulation of essential cellular processes. Like other cell types, epidermal cPLA2 may participate in various metabolic processes including eicosanoid generation. In this investigation, we demonstrated the presence of cPLA2 in guinea pig epidermis. The epidermal cPLA2 is Ca2+-dependent, active at micromolar concentration of Ca2+ and resistant to disulfide-reducing agents. Furthermore, it is inhibited by methyl arachidonyl fluorophosphonate (MAFP), a selective inhibitor of cPLA2, while 12-epi-scalardial (a sPLA2 inhibitor) did not cause inhibition. A test of several flavonoids revealed that quercetin (flavonol) weakly inhibited cPLA2, while flavanone had negligible inhibitory activity. In contrast, amentoflavone and ginkgetin (biflavones) markedly inhibited cPLA2 activity in the epidermis. These results underscore that different flavonoids do vary in their capability to exert differential effects on arachidonate metabolism in the skin via modulation of epidermal cPLA2 activity.
Kim
H R
HR
Colleges of Pharmacy, Kangweon National University, Korea.
Pham
H T
HT
Ziboh
V A
VA
D000818:Animals; D047310:Apigenin; D001095:Arachidonic Acids / Q000494:pharmacology; D044946:Biflavonoids; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology*; D044950:Flavanones; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011794:Quercetin / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D044946:Biflavonoids; D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D063065:Organophosphonates; C104810:methyl arachidonylfluorophosphonate; C077458:ginkgetin; D047310:Apigenin; C011164:amentoflavone; D011794:Quercetin; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium; C028610:flavanone