Undersulfated proteoglycans are secreted by cultured chondrocytes in the presence of the ionophore monensin.
The monovalent ionophore, monensin, inhibits secretion of many different proteins from a wide variety of cells. The site of blockage is at the golgi complex. We have exposed chick embryo chondrocytes in suspension culture to monensin, at concentrations ranging from 10(-8) to 10(-6) M. At the higher concentrations, between 10(-7) and 10(-6) M, monensin inhibited secretion of type II procollagen, which accumulated in the chondrocytes. At these concentrations of the ionophore, proteoglycan synthesis was inhibited, as measured by radioactive serine incorporation into core proteins and by radioactive glucosamine or SO4 incorporation into glycosaminoglycans. However, at a monensin concentration of 3 x 10(-8) M, the incorporations of serine and glucosamine were close to normal while SO4 incorporation was at 30% of control values. The ratio of glucosamine to serine in pronase-released glycosaminoglycans from culture media was unaffected by 3 x 10(-8) M monensin but the sulfate to serine ratio decreased to 29% of control values. Examination of the glycosaminoglycans by gel filtration showed a progressive increase in Kav values as sulfation decreased. Undersulfation was demonstrated by radiochromatographic analysis of the digestion products following incubation with chondroitinase ABC. The composite results show that monensin interferes with sulfation of newly synthesized proteoglycans.
D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D005663:Furans / Q000494:pharmacology*; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis; D008985:Monensin / Q000494:pharmacology*; D011347:Procollagen / Q000096:biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis*; D012694:Serine / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism
D005663:Furans; D006025:Glycosaminoglycans; D011347:Procollagen; D011509:Proteoglycans; D013431:Sulfates; C020341:glucosaminoglycans; D012694:Serine; D008985:Monensin; D005944:Glucosamine