Effects of lysosomal protease inhibitors on the degradation of acetylated low density lipoprotein in cultured rat peritoneal macrophages.
The effect of protease inhibitors, leupeptin and pepstatin A, on the metabolism of acetylated low density lipoprotein (acetyl-LDL) was investigated in cultured rat peritoneal macrophages and compared with that of chloroquine. While both leupeptin and pepstatin inhibited the proteolytic degradation of 125I-acetyl-LDL, a combination of both showed an additive effect. Similar to chloroquine, both protease inhibitors diminished [3H] oleate incorporation into cellular cholesteryl[3H] oleate and increased cholesterol content of macrophages. These results suggest that both thiol protease and cathepsin D participate in the physiological degradation of apolipoprotein in macrophages. The inhibition of apolipoprotein degradation seemed to have an effect on cholesterol metabolism in macrophages cultured with acetyl-LDL.
Kuroda
T
T
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yoshinari
M
M
Okamura
K
K
Okazawa
K
K
Ikenoue
H
H
Sato
K
K
Fujishima
M
M
D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007976:Leupeptins / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D010436:Pepstatins / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D007457:Iodine Radioisotopes; D007976:Leupeptins; D008077:Lipoproteins, LDL; D010436:Pepstatins; D011480:Protease Inhibitors; D014316:Tritium; C014195:Streptomyces pepsin inhibitor; D019301:Oleic Acid; D002784:Cholesterol; C032854:leupeptin; C031375:pepstatin