Shedding of sulfated lipids into gastric fluid and inhibition of pancreatic DNase I by cholesterol sulfate in concert with bile acids

Cholesterol sulfate (CS) and sulfatides in the epithelium of the digestive tract were found in the 1000 xg supernatants of digestive fluid, particular ly in gastric juices containing the duodenal contents and bile acids, there being 14-131 mu g of CS and 3-54 mu g of sulfatides per mg of protein in t he fluid, respectively. CS and sulfatides dissolved in detergents including bile acids inactivated pancreatic trypsin to the same level as by DMSO-sol ubilized sulfated lipids at 37 degrees C. Similarly, pancreatic DNase I was inhibited by CS solubilized with DMSO or bile acids, but not by sulfatides or other membrane lipids at 37 degrees C, Both the sulfate group and the h ydrophobic side chain of CS were indispensable structures for the inhibitio n of DNase I. Also, the optimum molar ratio of bile acids to CS was importa nt for expression of the inhibitory activity of CS toward DNase I, it being 0.18 of the optimum ratio for sodium taurocholate, and the molar ratio of CS to DNase I for complete inhibition was 342:1. Thus, CS was shown to play a role as an epithelial inhibitor of DNase I in concert with bile acids. ( C) 2000 Elsevier Science B.V. All rights reserved.