Therapy of severe familial heterozygous hypercholesterolemia by low-density lipoprotein apheresis with immunoadsorption: effects of the addition of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to therapy

1993 ◽  
Vol 71 (11) ◽  
Author(s):  
B.G. Jacob ◽  
W.O. Richter ◽  
P. Schwandt
Keyword(s):  
Coenzyme A ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Apheresis ◽  
Reductase Inhibitors ◽  
Coenzyme A Reductase

scholarly journals Chinese hamster cell mutant resistant to ML236B (Compactin) is defective in endocytosis of low-density lipo-protein.

1982 ◽  
Vol 2 (11) ◽  
pp. 1354-1361 ◽  
Author(s):  
A Masuda ◽  
S Akiyama ◽  
M Kuwano
Keyword(s):  
Coenzyme A ◽  
Spontaneous Mutation ◽  
Low Density Lipoprotein ◽  
Chinese Hamster ◽  
Specific Inhibitor ◽  
Density Lipoprotein ◽  
Chinese Hamster Cell ◽  
Cellular Level ◽  
Low Density ◽  
Coenzyme A Reductase

A fungal metabolite, ML236B (Compactin), isolated from Penicillium citrinum, is a specific inhibitor of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A reductase (EC 1.1.1.34). Three ML236B-resistant (ML236Br) mutants, MF-1, MF-2, and MF-3, were isolated from V79 after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The fluctuation test showed 2.2 X 10(-6) mutants per cell per generation of a spontaneous mutation frequency of ML236Br clones. These ML236Br clones showed a four- to fivefold-higher resistance to the drug than did their parental V79. Radioactive acetate, but not mevalonate, incorporation into the sterol fraction increased about 10-fold in ML236Br clones in comparison with that in V79. The cellular level of HMG-coenzyme A reductase in three ML236Br mutants was found to be a few-fold higher than that of V79 when cultured in the presence of lipoproteins. The 125I-labeled low-density lipoprotein-binding assay showed binding activity in three ML236Br clones comparable to that of the parental V79 cells. By contrast, an internalization assay of 125I-labeled low-density lipoprotein into the cells showed significantly reduced activity in three ML236Br clones in comparison with V79.

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