PUBLICATION
Structural and Functional Impairments of Reconstituted High-Density Lipoprotein by Incorporation of Recombinant β-Amyloid42
- Authors
- Cho, K.H.
- ID
- ZDB-PUB-210916-1
- Date
- 2021
- Source
- Molecules 26(14): (Journal)
- Registered Authors
- Keywords
- Alzheimer’s disease, apoA-I, beta-amyloid, dementia, high-density lipoproteins
- MeSH Terms
-
- Amyloid beta-Peptides/chemistry*
- Amyloid beta-Peptides/pharmacology
- Animals
- Apolipoprotein A-I/chemistry*
- Apolipoprotein A-I/pharmacology
- Humans
- Lipoproteins, HDL/chemistry*
- Lipoproteins, HDL/pharmacokinetics
- Peptide Fragments/chemistry*
- Peptide Fragments/pharmacology
- Phospholipids/chemistry*
- Phospholipids/metabolism
- Recombinant Proteins/chemistry
- Recombinant Proteins/pharmacology
- THP-1 Cells
- Zebrafish
- PubMed
- 34299592 Full text @ Molecules
Citation
Cho, K.H. (2021) Structural and Functional Impairments of Reconstituted High-Density Lipoprotein by Incorporation of Recombinant β-Amyloid42. Molecules. 26(14):.
Abstract
Beta (β)-amyloid (Aβ) is a causative protein of Alzheimer's disease (AD). In the pathogenesis of AD, the apolipoprotein (apo) A-I and high-density lipoprotein (HDL) metabolism is essential for the clearance of Aβ. In this study, recombinant Aβ42 was expressed and purified via the pET-30a expression vector and E.coli production system to elucidate the physiological effects of Aβ on HDL metabolism. The recombinant human Aβ protein (51 aa) was purified to at least 95% purity and characterized in either the lipid-free and lipid-bound states with apoA-I. Aβ was incorporated into the reconstituted HDL (rHDL) (molar ratio 95:5:1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol:apoA-I) with various apoA-I:Aβ ratios from 1:0 to 1:0.5, 1:1 and 1:2. With an increasing molar ratio of Aβ, the α-helicity of apoA-I was decreased from 62% to 36% with a red shift of the Trp wavelength maximum fluorescence from 337 to 340 nm in apoA-I. The glycation reaction of apoA-I was accelerated further by the addition of Aβ. The treatment of fructose and Aβ caused more multimerization of apoA-I in the lipid-free state and in HDL. The phospholipid-binding ability of apoA-I was impaired severely by the addition of Aβ in a dose-dependent manner. The phagocytosis of LDL into macrophages was accelerated more by the presence of Aβ with the production of more oxidized species. Aβ severely impaired tissue regeneration, and a microinjection of Aβ enhanced embryotoxicity. In conclusion, the beneficial functions of apoA-I and HDL were severely impaired by the addition of Aβ via its detrimental effect on secondary structure. The impairment of HDL functionality occurred more synergistically by means of the co-addition of fructose and Aβ.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping