Accumulation of glycolipids in mutant Chinese hamster ovary cells (Z65) with defective peroxisomal assembly and comparison of the metabolic rate of glycosphingolipids between Z65 cells and wild-type CHO-K1 cells

The influence of peroxisomal dysfunction on glycosphingolipid metabolism wa s investigated using mutant Chinese hamster ovary (CHO) cells (Z65) with de fective assembly of the peroxisomal membranes. In accordance with previous observations, the concentration of very long chain fatty acid (C24:0) was s hown to be higher in Z65 cells than in control cells. We then compared the composition of glycolipids in Z65 cells with that in CHO-K1 cells, which ar e wild-type Chinese hamster ovary cells with intact peroxisomes, and found significantly increased concentrations of ceramide monohexoside (CMH) and g anglioside GM3 in Z65 cells. However, there were no differences in the conc entrations of glycerophospholipids, triglycerides, free fatty acids and cho lesterol between Z65 and CHO-K1 cells. Further, to investigate the metaboli c rate of the major lipids, Z65 and CHO-K1 cells were pulse-labeled with [3 -C-14]serine. [3-C-14]Serine was incorporated into phosphatidylserine, phos phatidylethanolamine and sphingomyelin more quickly in CHO-K1 than in Z65 c ells. However, after 48 h, the radioactivity incorporated into those lipids , including CMH, was greater in Z65 cells than in CHO-K1 cells. Thus, the a ltered metabolism of glycosphingolipids, probably due to peroxisomal dysfun ction, was thought to be responsible for the change in glycosphingolipid co mposition in Z65 cells. (C) 1999 Elsevier Science B.V. All rights reserved.