Abstract
Redox-mediated modulation of cysteine (Cys) thiols has roles in various pathophysiological functions. We recently found that formation of disulfide-linked complexes of apolipoprotein (apo) E3 prevented apoE3 from irreversible oxidation. In this report, the influence of modification of Cys thiols in apoE2 and apoE3 on interactions with lipids was investigated. The apoE redox status was examined by a band-shift assay using a maleimide compound, and interactions with lipids were evaluated by a kinetic assay using dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and non-denaturing polyacrylamide gel electrophoresis. A reduction in DMPC clearance activity of apoE2 and apoE3 but not apoE4 was observed. Although hydrogen peroxide-induced oxidation decreased the clearance activity of the isoforms, apoE2 showed the greatest residual activity. Both Cys thiol masking and dimerization decreased the activity of apoE2 and apoE3 but not apoE4. In contrast, apoAII preincubation markedly increased the activity (apoE2 > apoE3 > apoE4), in accordance with the formation of apoE-AII and apoAII-E2-AII complexes. ApoAII preincubation also reduced the particle size of apoE-DMPC liposome complexes, especially for apoE2. Redox-mediated modification of Cys thiols of apoE2 or apoE3, especially disulfide bond formation with apoAII, affects lipid metabolism and consequently may be responsible for the diverse isoform specificity of apoE.
Acknowledgments
This research was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI, Grant Number 18K07461, Funder Id: http://dx.doi.org/10.13039/501100001691). Victoria Muir, PhD, from the Edanz Group (www.edanzediting.com/ac) edited a draft of this manuscript.
References
Anraku, M., Chuang, V.T., Maruyama, T., and Otagiri, M. (2013). Redox properties of serum albumin. Biochim. Biophys. Acta 1830, 5465–5472.10.1016/j.bbagen.2013.04.036Search in Google Scholar PubMed
Bassett, G.R., Gillard, B.K., and Pownall, H.J. (2012). Cholesterol determines and limits rHDL formation from human plasma apolipoprotein A-II and phospholipid membranes. Biochemistry 51, 8627–8635.10.1021/bi3011994Search in Google Scholar PubMed PubMed Central
Blanco-Vaca, F., Escolà-Gil, J.C., Martín-Campos, J.M., and Julve, J. (2001). Role of apoA-II in lipid metabolism and atherosclerosis: advances in the study of an enigmatic protein. J. Lipid. Res. 42, 1727–1739.10.1016/S0022-2275(20)31499-1Search in Google Scholar
Boutureira, O. and Bernardes, G.J. (2015). Advances in chemical protein modification. Chem. Rev. 115, 2174–2195.10.1021/cr500399pSearch in Google Scholar PubMed
Clay, M.A., Pyle, D.H., Rye, K.A., and Barter, P.J. (2000). Formation of spherical, reconstituted high density lipoproteins containing both apolipoproteins A-I and A-II is mediated by lecithin:cholesterol acyltransferase. J. Biol. Chem. 275, 9019–9025.10.1074/jbc.275.12.9019Search in Google Scholar PubMed
Cooper, C.E., Patel, R.P., Brookes, P.S., and Darley-Usmar, V.M. (2002). Nanotransducers in cellular redox signaling: modification of thiols by reactive oxygen and nitrogen species. Trends. Biochem. Sci. 27, 489–492.10.1016/S0968-0004(02)02191-6Search in Google Scholar
Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, G.W., Roses, A.D., Haines, J.L., and Pericak-Vance, M.A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261, 921–923.10.1126/science.8346443Search in Google Scholar PubMed
Garai, K., Baban, B., and Frieden, C. (2011). Dissociation of apolipoprotein E oligomers to monomer is required for high-affinity binding to phospholipid vesicles. Biochemistry 50, 2550–2558.10.1021/bi1020106Search in Google Scholar PubMed PubMed Central
Gillard, B.K., Lin, H.Y., Massey, J.B., and Pownall, H.J. (2009). Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells. Biochim. Biophys. Acta 1791, 1125–1132.10.1016/j.bbalip.2009.07.004Search in Google Scholar PubMed PubMed Central
Go, Y.M. and Jones, D.P. (2013). The redox proteome. J. Biol. Chem. 288, 26512–26520.10.1074/jbc.R113.464131Search in Google Scholar PubMed PubMed Central
Gong, J.S., Kobayashi, M., Hayashi, H., Zou, K., Sawamura, N., Fujita, S.C., Yanagisawa, K., and Michikawa, M. (2002). Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice. J. Biol. Chem. 277, 29919–29926.10.1074/jbc.M203934200Search in Google Scholar PubMed
Groitl, B. and Jakob, U. (2014). Thiol-based redox switches. Biochim. Biophys. Acta 1844, 1335–1343.10.1016/j.bbapap.2014.03.007Search in Google Scholar PubMed PubMed Central
Huang, Y. and Mahley, R.W. (2014). Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases. Neurobiol. Dis. 72, 3-12.10.1016/j.nbd.2014.08.025Search in Google Scholar PubMed PubMed Central
Innerarity, T.L., Hui, D.Y., Bersot, T.P., Mahley, R.W. (1986). Type III hyperlipoproteinemia: a focus on lipoprotein receptor-apolipoprotein E2 interactions. Adv. Exp. Med. Biol. 201, 273–288.10.1007/978-1-4684-1262-8_24Search in Google Scholar PubMed
Jayaraman, S., Gantz, D.L., and Gursky, O. (2005). Kinetic stabilization and fusion of apolipoprotein A-2:DMPC disks: comparison with apoA-1 and apoC-1. Biophys. J. 88, 2907–2918.10.1529/biophysj.104.055921Search in Google Scholar PubMed PubMed Central
Jolivalt, C., Leininger-Muller, B., Bertrand, P., Herber, R., Christen, Y., and Siest, G. (2000). Differential oxidation of apolipoprotein E isoforms and interaction with phospholipids. Free Radic. Biol. Med. 28, 129–140.10.1016/S0891-5849(99)00232-4Search in Google Scholar
Kawakami, A., Kubota, K., Yamada, N., Tagami, U., Takehana, K., Sonaka, I., Suzuki, E., and Hirayama, K. (2006). Identification and characterization of oxidized human serum albumin. A slight structural change impairs its ligand-binding and antioxidant functions. FEBS J. 273, 3346–3357.10.1111/j.1742-4658.2006.05341.xSearch in Google Scholar PubMed
Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.10.1038/227680a0Search in Google Scholar PubMed
Mahley, R.W. (1988). Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240, 622–630.10.1126/science.3283935Search in Google Scholar PubMed
Mahley, R.W. (2016). Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. J. Mol. Med. (Berl.) 94, 739–746.10.1007/s00109-016-1427-ySearch in Google Scholar PubMed PubMed Central
Mera, K., Anraku, M., Kitamura, K., Nakajou, K., Maruyama, T., and Otagiri, M. (2005). The structure and function of oxidized albumin in hemodialysis patients: its role in elevated oxidative stress via neutrophil burst. Biochem. Biophys. Res. Commun. 334, 1322–1328.10.1016/j.bbrc.2005.07.035Search in Google Scholar PubMed
Minagawa, H., Gong, J.S., Jung, C.G., Watanabe, A., Lund-Katz, S., Phillips, M.C., Saito, H., and Michikawa, M. (2009). Mechanism underlying apolipoprotein E (ApoE) isoform-dependent lipid efflux from neural cells in culture. J. Neurosci. Res. 87, 2498–2508.10.1002/jnr.22073Search in Google Scholar PubMed PubMed Central
Pitas, R.E., Boyles, J.K., Lee, S.H., Hui, D., and Weisgraber, K.H. (1987). Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J. Biol. Chem. 262, 14352–14360.10.1016/S0021-9258(18)47945-8Search in Google Scholar
Segall, M.L., Dhanasekaran, P., Baldwin, F., Anantharamaiah, G.M., Weisgraber, K.H., Phillips, M.C., and Lund-Katz, S. (2002). Influence of apoE domain structure and polymorphism on the kinetics of phospholipid vesicle solubilization. J. Lipid Res. 43, 1688–1700.10.1194/jlr.M200157-JLR200Search in Google Scholar PubMed
Thomas, J.A., Poland, B., and Honzatko, R. (1995). Protein sulfhydryls and their role in the antioxidant function of protein S-thiolation. Arch. Biochem. Biophys. 319, 1–9.10.1006/abbi.1995.1261Search in Google Scholar PubMed
Tozuka, M., Hidaka, H., Miyachi, M., Furihata, K., Katsuyama, T., and Kanai, M. (1992). Identification and characterization of apolipoprotein (AII-E2-AII) complex in human plasma lipoprotein. Biochim. Biophys. Acta 1165, 61–67.10.1016/0005-2760(92)90076-8Search in Google Scholar PubMed
Ulrich, K. and Jakob, U. (2019). The role of thiols in antioxidant systems. Free Radic. Biol. Med. 140, 14–27.10.1016/j.freeradbiomed.2019.05.035Search in Google Scholar PubMed PubMed Central
Weisgraber, K.H. and Mahley, R.W. (1978). Apoprotein (E--A-II) complex of human plasma lipoproteins. I. Characterization of this mixed disulfide and its identification in a high density lipoprotein subfraction. J. Biol. Chem. 253, 6281–6288.10.1016/S0021-9258(17)34612-4Search in Google Scholar
Weisgraber, K.H. (1990). Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112. J. Lipid Res. 31, 1503–1511.10.1016/S0022-2275(20)42621-5Search in Google Scholar
Yamauchi, K., Tozuka, M., Hidaka, H., Hidaka, E., Kondo, Y., and Katsuyama, T. (1999). Characterization of apolipoprotein E-containing lipoproteins in cerebrospinal fluid: effect of phenotype on the distribution of apolipoprotein E. Clin. Chem. 45, 1431–1438.10.1093/clinchem/45.9.1431Search in Google Scholar
Yamauchi, K., Tozuka, M., Hidaka, H., Nakabayashi, T., Sugano, M., Kondo, Y., and Katsuyama, T. (2000). Effect of apolipoprotein AII on the interaction of apolipoprotein E with beta-amyloid: some apo(E-AII) complexes inhibit the internalization of beta-amyloid in cultures of neuroblastoma cells. J. Neurosci. Res. 62, 608–614.10.1002/1097-4547(20001115)62:4<608::AID-JNR16>3.0.CO;2-4Search in Google Scholar
Yamauchi, K., Ebihara, Y., and Kawakami, Y. (2017). Redox status of serum apolipoprotein E and its impact on HDL cholesterol levels. Clin. Biochem. 50, 777–783.10.1016/j.clinbiochem.2017.03.021Search in Google Scholar
Yamauchi, K., Iwasaki, S., and Kawakami, Y. (2019). Redox equilibrium of serum apolipoprotein E3: a buffering effect of disulfide-linked complexes against oxidative stress on apolipoprotein E3-containing lipoproteins. Biosci. Rep. 39, BSR20190184, doi:10.1042/BSR20190184.10.1042/BSR20190184Search in Google Scholar
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2019-0414).
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Articles in the same Issue
- Frontmatter
- Reviews
- Power to the daughters – mitochondrial and mtDNA transmission during cell division
- Dr. NO and Mr. Toxic – the versatile role of nitric oxide
- Diffuse or hitch a ride: how photoreceptor lipidated proteins get from here to there
- Human papillomavirus oncoproteins and post-translational modifications: generating multifunctional hubs for overriding cellular homeostasis
- Research Articles/Short Communications
- Genes and Nucleic Acids
- LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147
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- The redox status of cysteine thiol residues of apolipoprotein E impacts on its lipid interactions
- Proteolysis
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