Effects of the ionophore monensin on type II collagen and proteoglycan synthesis and secretion by cultured chondrocytes.
Detailed studies of the effects of the ionophore monensin upon avian chondrocyte ultrastructure, macromolecular synthesis, and macromolecular secretion have been carried out. Embryonic avian chondrocytes in suspension culture were incubated in concentrations of monensin ranging from 1 X 10(-7) to 1 X 10(-6) M for durations up to 8 h. Electron microscopy revealed that the treated chondrocytes developed abnormal Golgi structures and a markedly distended rough endoplasmic reticulum. Biochemical and immunoassay studies showed that while total protein synthesis was only slightly impaired by monensin, the ionophore had pronounced effects upon the secretion of both type II collagen and proteoglycans. These two macromolecules responded to monensin inhibition in a similar fashion and accumulated within the affected chondrocytes. The kinetics of response over the monensin concentration range used was virtually identical for type II collagen and proteoglycan. Undersulfation of proteoglycan, caused by monensin, was examined by ion exchange chromatography and analysis of the products of chondroitinase ABC digestion. The results indicated that undersulfation affected all glycosaminoglycan chains in a general fashion rather than affecting a specific population of chains.
D000818:Animals; D002356:Cartilage / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis*; D005663:Furans / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000096:biosynthesis* / Q000302:isolation & purification; D007700:Kinetics; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*
D005663:Furans; D006025:Glycosaminoglycans; D011509:Proteoglycans; D003094:Collagen; D008985:Monensin