Increased cholesterol synthesis in Chinese hamster ovary cells deficient in peroxisomes.
In a previous study we have shown that Chinese hamster ovary (CHO) cells deficient in intact peroxisomes, lack the nonspecific lipid transfer protein (nsL-TP; sterol carrier protein 2) (van Heusden, G.P.H., Bos, K., Raetz, C.R.H. and Wirtz, K.W.A. (1990) J. Biol. Chem. 265, 4105-4110). The consequences of the absence of peroxisomes and of nsL-TP on intracellular cholesterol metabolism have been investigated in two peroxisome-deficient CHO cell lines (CHO-82 and CHO-78). Compared with wild-type cells (CHO-K1), the incorporation of [3H]acetate into cholesterol was 3-fold higher in the CHO-82 cells and 2-fold higher in the CHO-78 cells. In agreement with an increased synthesis of cholesterol, a 2-3-fold higher 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was measured in both mutant cell lines. On the other hand, addition of low density lipoprotein (LDL), mevalonate (30 mM) or 25-hydroxycholesterol (2 micrograms/ml) to cells grown in lipoprotein-deficient serum, demonstrated that in both mutant cell lines the down-regulation of HMG-CoA reductase and of cholesterol synthesis were comparable to that in wild-type cells. These results strongly suggest that, in addition to down-regulation by LDL-derived cholesterol, mevalonate and 25-hydroxycholesterol, HMG-CoA reductase activity is under control of peroxisomes and/or nsL-TP.
van Heusden
G P
GP
Center for Biomembranes and Lipid Enzymology, State University of Utrecht, Netherlands.
van Beckhoven
J R
JR
Thieringer
R
R
Raetz
C R
CR
Wirtz
K W
KW
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis*; D006224:Cricetinae; D003412:Cricetulus; D006888:Hydroxycholesterols / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology; D008830:Microbodies / Q000378:metabolism*; D010940:Plant Proteins
D000085:Acetates; D002352:Carrier Proteins; D006888:Hydroxycholesterols; D008077:Lipoproteins, LDL; D010940:Plant Proteins; C072087:sterol carrier proteins; C007997:25-hydroxycholesterol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid