OxHDL controls LOX-1 expression and plasma membrane localization through a mechanism dependent on NOX/ROS/NF-κB pathway on endothelial cells

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dc.contributor.authorPérez, Lorena
dc.contributor.authorVallejos, Alejandro
dc.contributor.authorEcheverria, Cesar
dc.contributor.authorVarela, Diego
dc.contributor.authorCabello-Verrugio, Claudio
dc.contributor.authorSimon, Felipe
dc.date.accessioned2024-07-02T19:06:32Z
dc.date.available2024-07-02T19:06:32Z
dc.date.issued2019-03-01
dc.descriptionIndexación: Scopus.
dc.description.abstractSystemic inflammatory diseases enhance circulating oxidative stress levels, which results in the oxidation of circulating high-density lipoprotein (oxHDL). Endothelial cell function can be negatively impacted by oxHDL, but the underlying mechanisms for this remain unclear. Some reports indicate that the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is also a receptor for oxHDL. However, it is unknown if oxHDL induces increased LOX-1 expression at the plasma membrane, as an event that supports endothelial dysfunction. Therefore, the aims of this study were to determine if oxHDL induces plasma-membrane level changes in LOX-1 and, if so, to describe the underlying mechanisms in endothelial cells. Our results demonstrate that the incubation of arterial or vein endothelial cells with oxHDL (and not HDL) induces the increase of LOX-1 expression at the plasma membrane; effect prevented by LOX-1 inhibition. Importantly, same results were observed in endothelial cells from oxHDL-treated rats. Furthermore, the observed oxHDL-induced LOX-1 expression is abolished by the down-regulation of NOX-2 expression with siRNA (and no others NOX isoforms), by the pharmacological inhibition of NAD(P)H oxidase (with DPI or apocynin) or by the inhibition of NF-κB transcription factor. Coherently, LOX-1 expression is augmented by the incubation of endothelial cells with H2O2 or GSSG even in absence of oxHDL, indicating that the NOX-2/ROS/ NF-κB axis is involved. Interestingly, oxHDL incubation also increases TNF-α expression, cytokine that induces LOX-1 expression. Thus, our results suggest a positive feedback mechanism for LOX-1 receptor during inflammatory condition where an oxidative burst will generate oxHDL from native HDL, activating LOX-1 receptor which in turn will increase the expression of NOX-2, TNF-α and LOX-1 receptor at the plasma membrane. In conclusion, oxHDL-induced translocation of LOX-1 to the plasma membrane could constitute an induction mechanism of endothelial dysfunction in systemic inflammatory diseases.
dc.description.urihttps://www.nature.com/articles/s41374-018-0151-3.pdf
dc.identifier.citationLaboratory Investigation Volume 99, Issue 3, Pages 421 - 437 1 March 2019
dc.identifier.doi10.1038/s41374-018-0151-3
dc.identifier.issn0023-6837
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/58168
dc.language.isoen_US
dc.publisherNature Publishing Group
dc.rights.licenseATRIBUCIÓN-NOCOMERCIAL-SINDERIVADAS 4.0 INTERNACIONAL
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/legalcode.es
dc.subjectAnimals
dc.subjectCell Membrane
dc.subjectCells, Cultured
dc.subjectEndothelial Cells
dc.subjectHuman Umbilical Vein Endothelial Cells
dc.subjectHumans
dc.subjectInflammation
dc.subjectLipoproteins, HDL
dc.subjectMale
dc.subjectNADPH Oxidase 2
dc.subjectNF-kappa B
dc.subjectOxidation-Reduction
dc.subjectOxidative Stress
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReactive Oxygen Species
dc.subjectScavenger Receptors, Class E
dc.subjectSignal Transduction
dc.titleOxHDL controls LOX-1 expression and plasma membrane localization through a mechanism dependent on NOX/ROS/NF-κB pathway on endothelial cells
dc.typeArtículo
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