Home Life Sciences The redox status of cysteine thiol residues of apolipoprotein E impacts on its lipid interactions
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The redox status of cysteine thiol residues of apolipoprotein E impacts on its lipid interactions

  • Kazuyoshi Yamauchi EMAIL logo and Yasushi Kawakami
Published/Copyright: January 8, 2020

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.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2019-0414).


Received: 2019-11-11
Accepted: 2020-01-03
Published Online: 2020-01-08
Published in Print: 2020-04-28

©2020 Walter de Gruyter GmbH, Berlin/Boston

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