Extralysosomal degradation of high-density lipoproteins in a human hepatoma cell line, Mahlavu.
Lipoprotein metabolism has been investigated in a novel human hepatoma cell line, Mahlavu, which has been reported to possess the characteristics of hepatocytes. Low-density lipoprotein (LDL) was degraded by Mahlavu cells. LDL taken up by the cells suppressed intracellular cholesterol biosynthesis and promoted cholesterol esterification in a manner similar to that of HepG2 cells. High-density lipoprotein (HDL) was also degraded by Mahlavu cells, whereas it was not degraded by fibroblasts. We compared the mode of intracellular metabolism of HDL to that of LDL. In contrast to the LDL receptor pathway, the degradation of HDL was not inhibited by 100 microM chloroquine added to the medium, indicating that the degradation may not occur in lysosomes. Cholesterol taken up as HDL-cholesterol by the Mahlavu cells had no effect on the intracellular biosynthesis of cholesterol nor on cholesterol esterification. The conditioned media in which Mahlavu cells had been cultured did not promote the degradation of HDL, suggesting that HDL is degraded intracellularly. These data suggest that HDL is taken up and degraded by the liver cells in contrast to extrahepatic peripheral cells such as fibroblasts and macrophages in which the degradation of HDL does not occur. The results indicate that HDL-associated cholesterol may be processed via a pathway different from that of LDL metabolism and that the degradation of HDL occurs extralysosomally.
Sakai
N
N
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Yamashita
S
S
Ueyama
Y
Y
Kawamoto
T
T
Nakamura
T
T
Funahashi
T
T
Kameda-Takemura
K
K
Kawata
S
S
Kubo
M
M
Tokunaga
K
K
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D002788:Cholesterol Esters / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008247:Lysosomes; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002788:Cholesterol Esters; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002738:Chloroquine