Publication
Title
Effect of lipid oxidation on the channel properties of Cx26 hemichannels : a molecular dynamics study
Author
Abstract
Intercellular communication plays a crucial role in cancer, as well as other diseases, such as inflammation, tissue degeneration, and neurological disorders. One of the proteins responsible for this, are connexins (Cxs), which come together to form a hemichannel. When two hemichannels of opposite cells interact with each other, they form a gap junction (GJ) channel, connecting the intracellular space of these cells. They allow the passage of ions, reactive oxygen and nitrogen species (RONS), and signaling molecules from the interior of one cell to another cell, thus playing an essential role in cell growth, differentiation, and homeostasis. The importance of GJs for disease induction and therapy development is becoming more appreciated, especially in the context of oncology. Studies have shown that one of the mechanisms to control the formation and disruption of GJs is mediated by lipid oxidation pathways, but the underlying mechanisms are not well understood. In this study, we performed atomistic molecular dynamics simulations to evaluate how lipid oxidation influences the channel properties of Cx26 hemichannels, such as channel gating and permeability. Our results demonstrate that the Cx26 hemichannel is more compact in the presence of oxidized lipids, decreasing its pore diameter at the extracellular side and increasing it at the amino terminus domains, respectively. The permeability of the Cx26 hemichannel for water and RONS molecules is higher in the presence of oxidized lipids. The latter may facilitate the intracellular accumulation of RONS, possibly increasing oxidative stress in cells. A better understanding of this process will help to enhance the efficacy of oxidative stress-based cancer treatments.
Language
English
Source (journal)
Archives of biochemistry and biophysics. - New York, N.Y., 1951, currens
Publication
New York, N.Y. : 2023
ISSN
0003-9861 [print]
1096-0384 [online]
DOI
10.1016/J.ABB.2023.109741
Volume/pages
746 (2023) , p. 1-12
Article Reference
109741
ISI
001079100300001
Pubmed ID
37689256
Full text (Publisher's DOI)
Full text (open access)
The author-created version that incorporates referee comments and is the accepted for publication version Available from 09.03.2024
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 30.10.2023
Last edited 21.11.2023
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