Glucocorticoid-induced phospholipase A2-inhibitory proteins mediate glucocorticoid teratogenicity in vitro.
Dexamethasone induces the synthesis of a phospholipase A2-inhibitory protein (PLIP) of molecular weight approximately equal to 55,000 from calf thymus and PLIPs of molecular weights 55,000, 40,000, 28,000, and 15,000 from A/J mouse thymus and from 12-day embryonic B10. A mouse palates. Sufficient quantities of calf thymus PLIP and of the 15,000 molecular weight mouse thymus and palate PLIPs were prepared and tested as inhibitors of programmed cell death in the medial-edge epithelium of single mouse embryonic palatal shelves in culture. All of the proteins tested prevent the loss of the medial-edge epithelium and, thus, produce the teratogenic effects of glucocorticoids in the palatal culture model. This teratogenic action of both PLIP and glucocorticoids is reversed by arachidonic acid, the precursor of prostaglandins and thromboxanes, suggesting that PLIP mediates the effects of glucocorticoids by inhibiting phospholipase A2.
D000818:Animals; D017302:Annexins; D002135:Calcium-Binding Proteins; D002417:Cattle; D003907:Dexamethasone / Q000633:toxicity*; D004622:Embryo, Mammalian; D006023:Glycoproteins; D006854:Hydrocortisone / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010159:Palate / Q000378:metabolism*; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D013045:Species Specificity; D013950:Thymus Gland / Q000378:metabolism*
D017302:Annexins; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D011506:Proteins; C030958:lipomodulin; D003907:Dexamethasone; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D006854:Hydrocortisone