EVIDENCE OF THE ROLE OF PROTEIN KINASE C IN PERINATAL DEVELOPMENT OF THE SURFACTANT SYNTHESIS

Abstract

Protein kinase C is a regulatory element in intracellular signal transduction. Diacylglycerol, produced in response to extracellular signals by turnover of phospholnosltldes, Ca++, and phosphatidylserine synerglstically activate protein kinase C. Phorbol esters, such as 12-0-tetradecanoylphorbol-13-acetate (TPA) directly activate protein kinase C. In this study we investigated whether 1) the degree of maturity influences the effect of inositol (INO) in potentiating the hormone-induced synthesis of surfactant phosphatidylcholine (SPC); 2) the INO effect is due to activation of protein kinase C. Lung explants from 21 or 28 day-old rabbit fetuses were cultured in serum-free minimal essential medium for 4 days in the presence of 0.1 μM dexamethasone (DX), 0.1 μM thyroxine (T4), 100 ng/ml TPA, or 1.5 mM INO. Choline incorporation into surfactant phosphatidylcholine (SPC) (CPM/μg DMA) was analyzed (mean+SD, n=4): TPA, diacylglycerol, or INO together with hormones, induced SPC synthesis in 21-day-old fetuses. In explants from 28-day-old fetuses, dibutyryl cyclic AMP was as effective as TPA in stimulating SPC incorporation. We propose that protein kinase C is involved In the differentiation of the surfactant system, and that high INO concentration facilitates intracellular transmission of hormonal signals in very immature alveolar cells.