Enhanced binding activity of an apolipoprotein E mutant, apo E5, to LDL receptors on human fibroblasts
Abstract
We have previously demonstrated an apolipoprotein E (apo E) mutant, apo E5, associated with hyperlipidemia and atherosclerotic vascular diseases. To investigate the possible mechanism of apo E5 involvement in the development of hyperlipidemia, we have isolated the apo E isoprotein and determined its binding activity to LDL (low density lipoprotein) receptors. It was shown that the apo E5 isoprotein was two times more active for binding to LDL receptors than apo E3. The concentration of apo E, at which 50% of 125I-labeled LDL bound to the receptor was displaced, was 29 ng/ml for apo E5 and 63 ng/ml for apo E3. This result suggests that the high affinity of apo E5 to LDL receptors results in a high uptake of apo E5-containing lipoproteins by the liver and leads to a down-regulation of LDL receptors in the liver. We can postulate that individuals with apo E5 are susceptible to hypercholesterolemia and in consequence to atherosclerosis.
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Previous studies have reported that apoE5 (Glu3Lys) is associated with hyperlipidemia and cardiovascular diseases.
“Previous studies have reported that apoE5 (Glu3Lys) is associated with hyperlipidemia and cardiovascular diseases”
From Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys) (2018) · cites this paper as [2]
ApoE5 (Glu3Lys) has higher (twofold greater) LDL receptor-binding activity than normal apoE3.
“but this isoform has higher LDL receptor-binding activity than that of normal apoE3.”
From Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys) (2018) · cites this paper as [2]
The pathogenic mechanisms underlying HLP in patients with apoE5 (Glu3Lys) are presumed to involve downregulation of LDL receptors due to high uptake of lipoproteins containing this apoE mutant.
“The pathogenic mechanisms underlying HLP in patients with apoE5 (Glu3Lys) are presumed to involve downregulation of low-density lipoprotein (LDL) receptors due to high uptake of lipoproteins containing this apoE mutant [10,11].”
From A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I (2018) · cites this paper as [10]
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Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys)
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- Authors
- Dong, L.-M., Yamamura, T., & Yamamoto, A.
- Affiliations
- National Cerebral and Cardiovascular Center (JP)
- Corresponding author
- Yamamura, Taku
- ORCID
- Yamamoto, Akira
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1990-04
- Volume
- 168
- Issue
- 2
- Pages
- 409-414
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2059811927
- Cited by
- 23
- References
- 5
- Citations by year
- 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- apolipoprotein E3, LDL receptor binding, hyperlipidemia, hypercholesterolemia, atherosclerosis, receptor down-regulation, hepatic lipoprotein uptake
- MeSH terms
- Apolipoproteins E, Arteriosclerosis, Dimyristoylphosphatidylcholine, Fibroblasts, Humans, Hyperlipidemias, Isoelectric Focusing, Mutation, Receptors, LDL
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