Metabolism of lipoproteins by human fetal hepatocytes
The rate of clearance of lipoproteins from plasma appears to play a role in the development of atherogenesis. The liver may account for as much as two thirds of the removal of low-density lipoprotein and one third of the clearance of high-density lipoprotein in certain animal species and humans, mainly by receptor-mediated pathways. The purpose of the present investigation was to determine if human fetal hepatocytes maintained in vitro take up and degrade lipoproteins. We first determined that the maximal binding capacity of iodine 125-iodo-LDL was approximately 300 ng of low-density lipoprotein protein/mg of membrane protein and an apparent dissociation constant of approximately 60 micrograms low-density lipoprotein protein/ml in membranes prepared from human fetal liver. We found that the maximal uptake of (/sup 125/I)iodo-LDL and (/sup 125/I)iodo-HDL by fetal hepatocytes occurred after 12 hours of incubation. Low-density lipoprotein uptake preceded the appearance of degradation products by 4 hours, and thereafter the degradation of low-density lipoprotein increased linearly for at least 24 hours. In contrast, high-density lipoprotein was not degraded to any extent by fetal hepatocytes. (/sup 125/I)Iodo-LDL uptake and degradation were inhibited more than 75% by preincubation with low-density lipoprotein but not significantly by high-density lipoprotein, whereas (/sup 125/I)iodo-HDL uptake was inhibited 70% by preincubation with high-density lipoprotein but not by low-density lipoprotein. In summary, human fetal hepatocytes take up and degrade low-density lipoprotein by a receptor-mediated process similar to that described for human extrahepatic tissues.
- Research Organization:
- Univ. of Texas Health Science Center, Dallas
- OSTI ID:
- 5471275
- Journal Information:
- Am. J. Obstet. Gynecol.; (United States), Vol. 157:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
LIPOPROTEINS
BLOOD-PLASMA CLEARANCE
METABOLISM
FETUSES
IN VITRO
IODINE 125
LIVER CELLS
MAN
MEMBRANE PROTEINS
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
CLEARANCE
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIPIDS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
SOMATIC CELLS
VERTEBRATES
550501* - Metabolism- Tracer Techniques