Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages

Hypercholesterolemia induces intracellular accumulation of cholesterol in macrophages and other immune cells, causing immunological dysfunctions. On cellular levels, cholesterol enrichment might lead to mitochondrial metabolic reprogramming and change macrophage functions. Additionally, as cholester...

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Autores principales:	Yi-Chou Chiu, Pei-Wen Chu, Hua-Ching Lin, Shau-Kwaun Chen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cholesterol Macrophage Oxidative phosphorylation Oxidative stress Inflammatory response Biology (General) QH301-705.5 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/3fbc3953698d48b6adbaadf12f476b94
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spelling	oai:doaj.org-article:3fbc3953698d48b6adbaadf12f476b942021-11-04T04:33:14ZAccumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages2405-580810.1016/j.bbrep.2021.101166https://doaj.org/article/3fbc3953698d48b6adbaadf12f476b942021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405580821002600https://doaj.org/toc/2405-5808Hypercholesterolemia induces intracellular accumulation of cholesterol in macrophages and other immune cells, causing immunological dysfunctions. On cellular levels, cholesterol enrichment might lead to mitochondrial metabolic reprogramming and change macrophage functions. Additionally, as cholesterol is permeable to the plasma membrane and might integrate into the membranous organelles, such as endoplasmic reticulum or mitochondria, cholesterol enrichment might change the functions or properties of these organelles, and ultimately alters the cellular functions. In this study, we investigate the mitochondrial alterations and intracellular oxidative stress induced by accumulation of cholesterol in the macrophages, and the possible immunological impacts caused by these alterations. Macrophage cells RAW264.7 were treated with cholesterol to induce intracellular accumulation of cholesterol, which further triggered the reduced production of reactive oxygen/nitrogen species, as well as decrease of oxidative phosphorylation. Basal respiration rate, ATP production and non-mitochondrial oxygen consumption are all suppressed. In contrast, glycolysis remained unaltered in this cholesterol-enriched condition. Previous studies demonstrated that metabolic profiles are associated with macrophage polarization. We further verified whether this metabolic reprogramming influences the macrophage responses to pro-inflammatory or anti-inflammatory stimuli. Our results showed the changes of transcriptional regulations in both pro-inflammatory and anti-inflammatory genes, but not specific toward M1 or M2 polarization. Collectively, the accumulation of cholesterol induced mitochondrial metabolic reprogramming and suppressed the production of oxidative stress, and induced the alterations of macrophage functions.Yi-Chou ChiuPei-Wen ChuHua-Ching LinShau-Kwaun ChenElsevierarticleCholesterolMacrophageOxidative phosphorylationOxidative stressInflammatory responseBiology (General)QH301-705.5BiochemistryQD415-436ENBiochemistry and Biophysics Reports, Vol 28, Iss , Pp 101166- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cholesterol Macrophage Oxidative phosphorylation Oxidative stress Inflammatory response Biology (General) QH301-705.5 Biochemistry QD415-436
spellingShingle	Cholesterol Macrophage Oxidative phosphorylation Oxidative stress Inflammatory response Biology (General) QH301-705.5 Biochemistry QD415-436 Yi-Chou Chiu Pei-Wen Chu Hua-Ching Lin Shau-Kwaun Chen Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages
description	Hypercholesterolemia induces intracellular accumulation of cholesterol in macrophages and other immune cells, causing immunological dysfunctions. On cellular levels, cholesterol enrichment might lead to mitochondrial metabolic reprogramming and change macrophage functions. Additionally, as cholesterol is permeable to the plasma membrane and might integrate into the membranous organelles, such as endoplasmic reticulum or mitochondria, cholesterol enrichment might change the functions or properties of these organelles, and ultimately alters the cellular functions. In this study, we investigate the mitochondrial alterations and intracellular oxidative stress induced by accumulation of cholesterol in the macrophages, and the possible immunological impacts caused by these alterations. Macrophage cells RAW264.7 were treated with cholesterol to induce intracellular accumulation of cholesterol, which further triggered the reduced production of reactive oxygen/nitrogen species, as well as decrease of oxidative phosphorylation. Basal respiration rate, ATP production and non-mitochondrial oxygen consumption are all suppressed. In contrast, glycolysis remained unaltered in this cholesterol-enriched condition. Previous studies demonstrated that metabolic profiles are associated with macrophage polarization. We further verified whether this metabolic reprogramming influences the macrophage responses to pro-inflammatory or anti-inflammatory stimuli. Our results showed the changes of transcriptional regulations in both pro-inflammatory and anti-inflammatory genes, but not specific toward M1 or M2 polarization. Collectively, the accumulation of cholesterol induced mitochondrial metabolic reprogramming and suppressed the production of oxidative stress, and induced the alterations of macrophage functions.
format	article
author	Yi-Chou Chiu Pei-Wen Chu Hua-Ching Lin Shau-Kwaun Chen
author_facet	Yi-Chou Chiu Pei-Wen Chu Hua-Ching Lin Shau-Kwaun Chen
author_sort	Yi-Chou Chiu
title	Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages
title_short	Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages
title_full	Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages
title_fullStr	Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages
title_full_unstemmed	Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages
title_sort	accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/3fbc3953698d48b6adbaadf12f476b94
work_keys_str_mv	AT yichouchiu accumulationofcholesterolsuppressesoxidativephosphorylationandalteredresponsestoinflammatorystimuliofmacrophages AT peiwenchu accumulationofcholesterolsuppressesoxidativephosphorylationandalteredresponsestoinflammatorystimuliofmacrophages AT huachinglin accumulationofcholesterolsuppressesoxidativephosphorylationandalteredresponsestoinflammatorystimuliofmacrophages AT shaukwaunchen accumulationofcholesterolsuppressesoxidativephosphorylationandalteredresponsestoinflammatorystimuliofmacrophages
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Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages

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