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Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case

Peroxidation of unsaturated phospholipids, glycolipids, and cholesterol in biological membranes under oxidative stress conditions can underlie a variety of pathological conditions, including atherogenesis, neurodegeneration, and carcinogenesis. Lipid hydroperoxides (LOOHs) are key intermediates in t...

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Autores principales: Girotti, Albert W., Korytowski, Witold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379493/
https://www.ncbi.nlm.nih.gov/pubmed/34418596
http://dx.doi.org/10.1016/j.redox.2021.102096
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author Girotti, Albert W.
Korytowski, Witold
author_facet Girotti, Albert W.
Korytowski, Witold
author_sort Girotti, Albert W.
collection PubMed
description Peroxidation of unsaturated phospholipids, glycolipids, and cholesterol in biological membranes under oxidative stress conditions can underlie a variety of pathological conditions, including atherogenesis, neurodegeneration, and carcinogenesis. Lipid hydroperoxides (LOOHs) are key intermediates in the peroxidative process. Nascent LOOHs may either undergo one-electron reduction to exacerbate membrane damage/dysfunction or two-electron reduction to attenuate this. Another possibility is LOOH translocation to an acceptor site, followed by either of these competing reductions. Cholesterol (Ch)-derived hydroperoxides (ChOOHs) have several special features that will be highlighted in this review. In addition to being susceptible to one-electron vs. two-electron reduction, ChOOHs can translocate from a membrane of origin to another membrane, where such turnover may ensue. Intracellular StAR family proteins have been shown to deliver not only Ch to mitochondria, but also ChOOHs. StAR-mediated transfer of free radical-generated 7-hydroperoxycholesterol (7-OOH) results in impairment of (a) Ch utilization in steroidogenic cells, and (b) anti-atherogenic reverse Ch transport in vascular macrophages. This is the first known example of how a peroxide derivative can be recognized by a natural lipid trafficking pathway with deleterious consequences. For each example above, we will discuss the underlying mechanism of oxidative damage/dysfunction, and how this might be mitigated by antioxidant intervention.
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spelling pubmed-83794932021-08-27 Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case Girotti, Albert W. Korytowski, Witold Redox Biol Review Article Peroxidation of unsaturated phospholipids, glycolipids, and cholesterol in biological membranes under oxidative stress conditions can underlie a variety of pathological conditions, including atherogenesis, neurodegeneration, and carcinogenesis. Lipid hydroperoxides (LOOHs) are key intermediates in the peroxidative process. Nascent LOOHs may either undergo one-electron reduction to exacerbate membrane damage/dysfunction or two-electron reduction to attenuate this. Another possibility is LOOH translocation to an acceptor site, followed by either of these competing reductions. Cholesterol (Ch)-derived hydroperoxides (ChOOHs) have several special features that will be highlighted in this review. In addition to being susceptible to one-electron vs. two-electron reduction, ChOOHs can translocate from a membrane of origin to another membrane, where such turnover may ensue. Intracellular StAR family proteins have been shown to deliver not only Ch to mitochondria, but also ChOOHs. StAR-mediated transfer of free radical-generated 7-hydroperoxycholesterol (7-OOH) results in impairment of (a) Ch utilization in steroidogenic cells, and (b) anti-atherogenic reverse Ch transport in vascular macrophages. This is the first known example of how a peroxide derivative can be recognized by a natural lipid trafficking pathway with deleterious consequences. For each example above, we will discuss the underlying mechanism of oxidative damage/dysfunction, and how this might be mitigated by antioxidant intervention. Elsevier 2021-08-08 /pmc/articles/PMC8379493/ /pubmed/34418596 http://dx.doi.org/10.1016/j.redox.2021.102096 Text en © 2021 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review Article
Girotti, Albert W.
Korytowski, Witold
Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case
title Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case
title_full Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case
title_fullStr Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case
title_full_unstemmed Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case
title_short Pathophysiological potential of lipid hydroperoxide intermembrane translocation: Cholesterol hydroperoxide translocation as a special case
title_sort pathophysiological potential of lipid hydroperoxide intermembrane translocation: cholesterol hydroperoxide translocation as a special case
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379493/
https://www.ncbi.nlm.nih.gov/pubmed/34418596
http://dx.doi.org/10.1016/j.redox.2021.102096
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