TY - JOUR
T1 - Regulation of the activity of the low density lipoprotein receptor in human fibroblasts
AU - Brown, Michael S.
AU - Goldstein, Joseph L.
N1 - Funding Information:
We thank Mary Sobhani for her excellent technical assistance. Jean Helgeson and Helen Bohmfalk provided excellent assistance with the cell culture. This work was supported by research grants from the NIH and the American Heart Association. M.S.B. is an established investigator of the American Heart Association. J.L.G. is the recipient of a USPHS Research Career Development Award.
PY - 1975/11
Y1 - 1975/11
N2 - A specific receptor on the surface of cultured human fibroblasts binds plasma low density lipoprotein (LDL) with high affinity, and thereby initiates a cellular process by which the LDL is internalized and degraded within lysosomes and its cholesterol component is made available for cellular membrane synthesis. Current studies demonstrate that the activity of this LDL receptor is under feedback regulation. Prior incubation of fibroblast monolayers with cholesterol, 25-hydroxycholesterol, or LDL progressively reduced the ability of the cells to bind 125I-labeled LDL at the high affinity site. A series of kinetic studies indicated that this reduction in binding was due to a decrease in the number of LDL receptors. From measurements of the rate of decline in 125I-LDL binding activity after administration of cycloheximide, the LDL receptor was calculated to have a half-life of about 25 hr. LDL appeared to reduce 125I-LDL-binding activity by suppressing the synthesis of receptor molecules. Thus cultured human fibroblasts regulate their intracellular cholesterol content by regulating the activity of the LDL receptor, which in turn controls the rate of cellular entry of cholesterol derived from plasma LDL contained within the culture medium.
AB - A specific receptor on the surface of cultured human fibroblasts binds plasma low density lipoprotein (LDL) with high affinity, and thereby initiates a cellular process by which the LDL is internalized and degraded within lysosomes and its cholesterol component is made available for cellular membrane synthesis. Current studies demonstrate that the activity of this LDL receptor is under feedback regulation. Prior incubation of fibroblast monolayers with cholesterol, 25-hydroxycholesterol, or LDL progressively reduced the ability of the cells to bind 125I-labeled LDL at the high affinity site. A series of kinetic studies indicated that this reduction in binding was due to a decrease in the number of LDL receptors. From measurements of the rate of decline in 125I-LDL binding activity after administration of cycloheximide, the LDL receptor was calculated to have a half-life of about 25 hr. LDL appeared to reduce 125I-LDL-binding activity by suppressing the synthesis of receptor molecules. Thus cultured human fibroblasts regulate their intracellular cholesterol content by regulating the activity of the LDL receptor, which in turn controls the rate of cellular entry of cholesterol derived from plasma LDL contained within the culture medium.
UR - http://www.scopus.com/inward/record.url?scp=0016679756&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0016679756&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(75)90182-8
DO - 10.1016/0092-8674(75)90182-8
M3 - Article
C2 - 212203
AN - SCOPUS:0016679756
SN - 0092-8674
VL - 6
SP - 307
EP - 316
JO - Cell
JF - Cell
IS - 3
ER -