Structural and Functional Impairments of Reconstituted High-Density Lipoprotein by Incorporation of Recombinant β-Amyloid42
Abstract
:1. Introduction
2. Results
2.1. Purification and Characterization of Aβ42
2.2. Structural Characteristics of rHDL Containing Aβ
2.3. Glycation of apoA-I and HDL3 Were Accelerated by Aβ
2.4. Aβ Caused More Rapid Isothermal Denaturation of rHDL
2.5. More LDL Phagocytosis into Macrophage by Aβ
2.6. Toxicity on Embryo and Tissue Regeneration of Aβ
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Expression and Purification of Aβ
4.3. Protein Sequencing
4.4. Characterization of Secondary Structure
4.5. Characterization of Trp Fluorescence during Isothermal Denaturation
4.6. Purification of Lipoproteins
4.7. Purification of Human apoA-I
4.8. Oxidation of LDL
4.9. Synthesis of Reconstituted HDL
4.10. Phospholipid Binding Assay
4.11. Glycation of apoA-I with Aβ
4.12. Western Blotting
4.13. LDL Phagocytosis Assay
4.14. Zebrafish
4.15. Microinjection of Zebrafish Embryos
4.16. Fin Regeneration
4.17. Statistical Analysis
5. Conclusions
Supplementary Materials
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
- Svensson, T.; Sawada, N.; Mimura, M.; Nozaki, S.; Shikimoto, R.; Tsugane, S. The association between midlife serum high-density lipoprotein and mild cognitive impairment and dementia after 19 years of follow-up. Transl. Psychiatry 2019, 9, 26. [Google Scholar] [CrossRef]
- Demarin, V.; Lisak, M.; Morović, S.; Cengić, T. Low high-density lipoprotein cholesterol as the possible risk factor for stroke. Acta Clin. Croat. 2010, 49, 429–439. [Google Scholar]
- Justin, B.N.; Turek, M.; Hakim, A.M. Heart disease as a risk factor for dementia. Clin. Epidemiol. 2013, 5, 135–145. [Google Scholar] [CrossRef] [Green Version]
- Deckers, K.; Schievink, S.H.J.; Rodriquez, M.M.F.; van Oostenbrugge, R.J.; van Boxtel, M.P.J.; Verhey, F.R.J.; Köhler, S. Coronary heart disease and risk for cognitive impairment or dementia: Systematic review and meta-analysis. PLoS ONE 2017, 12, e0184244. [Google Scholar] [CrossRef]
- Craft, S. The role of metabolic disorders in Alzheimer disease and vascular dementia. Arch. Neurol. 2009, 66, 300–305. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koudinov, A.R.; Berezov, T.T.; Kumar, A.; Koudinova, N.V. Alzheimer’s amyloid b interaction with normal human plasma high density lipoprotein: Association with apolipoprotein and lipids. Clin. Chim. Acta 1998, 270, 75–84. [Google Scholar] [CrossRef]
- Paula-Lima, A.C.; Tricerri, M.A.; Brito-Moreira, J.; Bomfim, T.R.; Oliveira, F.F.; Magdesian, M.H.; Grinberg, L.T.; Panizzutti, R.; Ferreira, S.T. Human apolipoprotein A-I binds amyloid-beta and prevents Abeta-induced neurotoxicity. Int. J. Biochem. Cell Biol. 2009, 41, 1361–1370. [Google Scholar] [CrossRef] [PubMed]
- Rohrer, L.; Hersberger, M.; von Eckardstein, A. High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease. Curr. Opin. Lipidol. 2004, 15, 269–278. [Google Scholar] [CrossRef] [PubMed]
- Kosmas, C.E.; Martinez, I.; Sourlas, A.; Bouza, K.V.; Campos, F.N.; Torres, V.; Montan, P.D.; Guzman, E. High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease. Drugs Context 2018, 7, 212525. [Google Scholar] [CrossRef] [PubMed]
- Kosmas, C.E.; Christodoulidis, G.; Cheng, J.W.; Vittorio, T.J.; Lerakis, S. High-density lipoprotein functionality in coronary artery disease. Am. J. Med. Sci. 2014, 347, 504–508. [Google Scholar] [CrossRef]
- Yang, Y.; Song, W. Molecular links between Alzheimer’s disease and diabetes mellitus. Neuroscience 2013, 250, 140–150. [Google Scholar] [CrossRef]
- Chou, P.S.; Wu, M.N.; Yang, C.C.; Shen, C.T.; Yang, Y.H. Effect of advanced glycation end products on the progression of Alzheimer’s disease. J. Alzheimers Dis. 2019, 72, 191–197. [Google Scholar] [CrossRef]
- Cho, K.H.; Kim, J.R.; Lee, I.C.; Kwon, H.J. Native high-density lipoproteins (HDL) with higher Paraoxonase exerts a potent antiviral effect against SARS-CoV-2 (COVID-19), while glycated HDL lost the antiviral activity. Antioxidants 2021, 10, 209. [Google Scholar] [CrossRef]
- Liu, D.; Ji, L.; Zhang, D.; Tong, X.; Pan, B.; Liu, P.; Zhang, Y.; Huang, Y.; Su, J.; Willard, B.; et al. Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity. Diabetes Metab. Res. Rev. 2012, 28, 186–195. [Google Scholar] [CrossRef]
- Soran, H.; Hama, S.; Yadav, R.; Durrington, P.N. HDL functionality. Curr. Opin. Lipidol. 2012, 23, 353–366. [Google Scholar] [CrossRef] [PubMed]
- Ruiz-Ramie, J.J.; Barber, J.L.; Sarzynski, M.A. Effects of exercise on HDL functionality. Curr. Opin. Lipidol. 2019, 30, 16–23. [Google Scholar] [CrossRef] [PubMed]
- Cho, K.H. High-Density Lipoproteins as Biomarkers and Therapeutic Tools: Volume 2. Improvement and Enhancement of HDL and Clinical Applications, 1st ed.; Springer: New York, NY, USA, 2019. [Google Scholar]
- Vitali, C.; Wellington, C.L.; Calabresi, L. HDL and cholesterol handling in the brain. Cardiovasc. Res. 2014, 103, 405–413. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, A.L.; Swaminathan, S.K.; Curran, G.L.; Poduslo, J.F.; Lowe, V.J.; Li, L.; Kandimalla, K.K. Apolipoprotein A-I crosses the blood–brain barrier through clathrin-independent and cholesterol-mediated endocytosis. J. Pharmacol. Exp. Ther. 2019, 369, 481–488. [Google Scholar] [CrossRef]
- Koldamova, R.P.; Lefterov, I.M.; Lazo, J.S. Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits A beta aggregation and toxicity. Biochemistry 2001, 40, 3553–3560. [Google Scholar] [CrossRef]
- Currò, M.; Risitano, R.; Ferlazzo, N.; Cirmi, S.; Gangemi, C.; Caccamo, D.; Ientile, R.; Navarra, M. Citrus bergamia Juice Extract Attenuates β-Amyloid-Induced Pro-Inflammatory Activation of THP-1 Cells Through MAPK and AP-1 Pathways. Sci. Rep. 2016, 6, 20809. [Google Scholar] [CrossRef] [Green Version]
- Merched, A.; Xia, Y.; Visvikis, S.; Serot, J.M.; Siest, G. Decreased high-density lipoprotein cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer’s disease. Neurobiol. Aging 2000, 21, 27–30. [Google Scholar] [CrossRef]
- Shih, Y.H.; Tsai, K.J.; Lee, C.W.; Shiesh, S.C.; Chen, W.T.; Pai, M.C.; Kuo, Y.M. Apolipoprotein C-III is an amyloid-β-binding protein and an early marker for Alzheimer’s disease. J. Alzheimers Dis. 2014, 41, 855–865. [Google Scholar] [CrossRef] [PubMed]
- Xie, C.; Lund, E.G.; Turley, S.D.; Russell, D.W.; Dietschy, J.M. Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration. J. Lipid Res. 2003, 44, 1780–1789. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dietschy, J.M.; Turley, S.D. Cholesterol metabolism in the brain. Curr. Opin. Lipidol. 2001, 12, 105–112. [Google Scholar] [CrossRef] [PubMed]
- Bahrami, A.; Barreto, G.E.; Lombardi, G.; Pirro, M.; Sahebkar, A. Emerging roles for high-density lipoproteins in neurodegenerative disorders. BioFactors 2019, 45, 725–739. [Google Scholar] [CrossRef] [PubMed]
- Wilson, L.M.; Pham, C.L.; Jenkins, A.J.; Wade, J.D.; Hill, A.F.; Perugini, M.A.; Howlett, G.J. High density lipoproteins bind Abeta and apolipoprotein C-II amyloid fibrils. J. Lipid Res. 2006, 47, 755–760. [Google Scholar] [CrossRef] [Green Version]
- Robert, J.; Stukas, S.; Button, E.; Cheng, W.H.; Lee, M.; Fan, J.; Wilkinson, A.; Kulic, I.; Wright, S.D.; Wellington, C.L. Reconstituted high-density lipoproteins acutely reduce soluble brain Aβ levels in symptomatic APP/PS1 mice. Biochim. Biophys. Acta 2016, 1862, 1027–1036. [Google Scholar] [CrossRef] [PubMed]
- Lovestone, S.; Smith, U. Advanced glycation end products, dementia, and diabetes. Proc. Natl. Acad. Sci. USA 2014, 111, 4743–4744. [Google Scholar] [CrossRef] [Green Version]
- Fica-Contreras, S.M.; Shuster, S.O.; Durfee, N.D.; Bowe, G.J.K.; Henning, N.J.; Hill, S.A.; Vrla, G.D.; Stillman, D.R.; Suralik, K.M.; Sandwick, R.K.; et al. Glycation of Lys-16 and Arg-5 in amyloid-β and the presence of Cu2+ play a major role in the oxidative stress mechanism of Alzheimer’s disease. J. Biol. Inorg. Chem. 2017, 22, 1211–1222. [Google Scholar] [CrossRef]
- Münch, G.; Thome, J.; Foley, P.; Schinzel, R.; Riederer, P. Advanced glycation endproducts in ageing and Alzheimer’s disease. Brain Res. Rev. 1997, 23, 134–143. [Google Scholar] [CrossRef]
- Park, K.H.; Kim, J.M.; Cho, K.H. Elaidic acid (EA) generates dysfunctional high-density lipoproteins and consumption of EA exacerbates hyperlipidemia and fatty liver change in zebrafish. Mol. Nutr. Food Res. 2014, 58, 1537–1545. [Google Scholar] [CrossRef]
- Honda, T.; Ohara, T.; Shinohara, M.; Hata, J.; Toh, R.; Yoshida, D.; Shibata, M.; Ishida, T.; Hirakawa, Y.; Irino, Y.; et al. Serum elaidic acid concentration and risk of dementia: The Hisayama Study. Neurology 2019, 93, e2053–e2064. [Google Scholar] [CrossRef] [PubMed]
- Chernick, D.; Zhong, R.; Li, L. The role of HDL and HDL mimetic peptides as potential therapeutics for Alzheimer’s disease. Biomolecules 2020, 10, 1276. [Google Scholar] [CrossRef] [PubMed]
- Matsudaira, P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J. Biol. Chem. 1987, 262, 10035–10038. [Google Scholar] [CrossRef]
- Chen, Y.H.; Yang, J.T.; Martinez, H.M. Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion. Biochemistry 1972, 11, 4120–4131. [Google Scholar] [CrossRef]
- Han, J.M.; Jeong, T.S.; Lee, W.S.; Choi, I.; Cho, K.H. Structural and functional properties of V156K and A158E mutants of apolipoprotein A-I in the lipid-free and lipid-bound states. J. Lipid Res. 2005, 46, 589–596. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cho, K.H.; Jonas, A. A key point mutation (V156E) affects the structure and functions of human Apolipoprotein A-I. J. Biol. Chem. 2000, 275, 26821–26827. [Google Scholar] [CrossRef]
- Park, K.H.; Shin, D.G.; Kim, J.R.; Cho, K.H. Senescence-related truncation and multimerization of apolipoprotein A-I in high-density lipoprotein with an elevated level of advanced glycated end products and cholesteryl ester transfer activity. J. Gerontol. A Biol. Sci. Med. Sci. 2010, 65, 600–610. [Google Scholar] [CrossRef] [Green Version]
- Havel, R.J.; Eder, H.A.; Bragdon, J.H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Investig. 1955, 34, 1345–1353. [Google Scholar] [CrossRef] [Green Version]
- Brewer, H.B., Jr.; Ronan, R.; Meng, M.; Bishop, C. Isolation and characterization of apolipoproteins A-I, A-II and A-IV. Methods Enzymol. 1986, 128, 223–246. [Google Scholar] [CrossRef] [PubMed]
- Blois, M.S. Antioxidant determinations by the use of a stable free radical. Nature 1958, 181, 1199–1200. [Google Scholar] [CrossRef]
- Cho, K.H. Synthesis of reconstituted high density lipoprotein (rHDL) containing apoA-I and apoC-III: The functional role of apoC-III in rHDL. Mol. Cells 2009, 27, 291–297. [Google Scholar] [CrossRef] [PubMed]
- Pownall, H.J.; Massey, J.B.; Kusserow, S.K.; Gotto, A.M., Jr. Kinetics of lipid—Protein interactions: Effect of cholesterol on the association of human plasma high-density apolipoprotein A-I with L-alpha-dimyristoylphosphatidylcholine. Biochemistry 1979, 18, 574–579. [Google Scholar] [CrossRef] [PubMed]
- Park, K.H.; Jang, W.; Kim, K.Y.; Kim, J.R.; Cho, K.H. Fructated apolipoprotein A-I showed severe structural modification and loss of beneficial functions in lipid-free and lipid-bound state with acceleration of atherosclerosis and senescence. Biochem. Biophys. Res. Commun. 2010, 392, 295–300. [Google Scholar] [CrossRef]
- McPherson, J.D.; Shilton, B.H.; Walton, D.J. Role of fructose in glycation and cross-linking of proteins. Biochemistry 1988, 27, 1901–1907. [Google Scholar] [CrossRef] [PubMed]
- Markwell, M.A.; Haas, S.M.; Bieber, L.L.; Tolbert, N.E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal. Biochem. 1978, 87, 206–210. [Google Scholar] [CrossRef]
Molar Composition (POPC:FC:apoA-I:Aβ) | WMF a (nm) | α-Helicity b (%) | Size (Å) c | |
---|---|---|---|---|
apoA-I-rHDL | 95:5:1:0 | 337.5 | 62.3 | 97 |
rHDL (apoA-I:Aβ) | 95:5:1:0.5 | 339.2 | 48.0 | 96 |
95:5:1:1 | 339.4 | 44.7 | 95 | |
95:5:1:2 | 340.6 | 36.2 | 93 | |
95:5:0:1 | ND | 10.5 | ND |
0 M Urea | 1 M Urea | 2 M Urea | 3 M Urea | 4 M Urea | 5 M Urea | |
---|---|---|---|---|---|---|
Lipid-free apoA-I | 339.7 ± 0.4 | 343.8 ± 1.0 | 347.8 ± 0.1 | 353.8 ± 0.4 | 355.3 ± 0.5 | 355.7 ± 1.0 |
rHDL- (apoA-I: Aβ, 1:0) | 338.5 ± 0.3 | 340.3 ± 0.5 | 340.5 ± 0.7 | 338.7 ± 0.3 | 340.7 ± 0.5 | 347.2 ± 0.7 |
rHDL- (apoA-I:Aβ, 1:0.5) | 339.5 ± 0.3 | 339.0 ± 0.6 | 341.5 ± 0.3 | 342.2 ± 0.6 | 344.4 ± 0.4 | 346.2 ± 0.1 |
rHDL- (apoA-I:Aβ, 1:1) | 339.0 ± 0.1 | 340.0 ± 0.7 | 339.3 ± 0.2 | 342.0 ± 0.1 | 345.0 ± 0.4 | 346.2 ± 0.2 |
rHDL- (apoA-I:Aβ, 1:2) | 341.5 ± 0.3 | 343.0 ± 0.4 | 344.0 ± 1.1 | 344.0 ± 0.1 | 344.0 ± 0.3 | 346.0 ± 0.4 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Cho, K.-H. Structural and Functional Impairments of Reconstituted High-Density Lipoprotein by Incorporation of Recombinant β-Amyloid42. Molecules 2021, 26, 4317. https://doi.org/10.3390/molecules26144317
Cho K-H. Structural and Functional Impairments of Reconstituted High-Density Lipoprotein by Incorporation of Recombinant β-Amyloid42. Molecules. 2021; 26(14):4317. https://doi.org/10.3390/molecules26144317
Chicago/Turabian StyleCho, Kyung-Hyun. 2021. "Structural and Functional Impairments of Reconstituted High-Density Lipoprotein by Incorporation of Recombinant β-Amyloid42" Molecules 26, no. 14: 4317. https://doi.org/10.3390/molecules26144317