Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium

Vascular aging is accompanied by increases in circulatory proinflammatory cytokines leading to inflammatory endothelial response implicated in early atherogenesis. To study the possible role of mitochondria-derived reactive oxygen species (ROS) in this phenomenon, we applied the effective mitochondr...

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Main Authors:	Zinovkin, Roman A., Romaschenko, Valeria P., Galkin, Ivan I., Zakharova, Vlada V., Pletjushkina, Olga Yu., Chernyak, Boris V., Popova, Ekaterina N.
Format:	Online
Language:	English
Published:	Impact Journals LLC 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169860/

id	pubmed-4169860
recordtype	oai_dc
spelling	pubmed-41698602014-09-22 Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium Zinovkin, Roman A. Romaschenko, Valeria P. Galkin, Ivan I. Zakharova, Vlada V. Pletjushkina, Olga Yu. Chernyak, Boris V. Popova, Ekaterina N. Research Paper Vascular aging is accompanied by increases in circulatory proinflammatory cytokines leading to inflammatory endothelial response implicated in early atherogenesis. To study the possible role of mitochondria-derived reactive oxygen species (ROS) in this phenomenon, we applied the effective mitochondria-targeted antioxidant SkQ1, the conjugate of plastoquinone with dodecyltriphenylphosphonium. Eight months treatment of (CBAxC57BL/6) F1 mice with SkQ1 did not prevent age-related elevation of the major proinflammatory cytokines TNF and IL-6 in serum, but completely abrogated the increase in adhesion molecule ICAM1 expression in aortas of 24-month-old animals. In endothelial cell culture, SkQ1 also attenuated TNF-induced increase in ICAM1, VCAM, and E-selectin expression and secretion of IL-6 and IL-8, and prevented neutrophil adhesion to the endothelial monolayer. Using specific inhibitors to transcription factor NF-κB and stress-kinases p38 and JNK, we demonstrated that TNF-induced ICAM1 expression depends mainly on NF-κB activity and, to a lesser extent, on p38. SkQ1 had no effect on p38 phosphorylation (activation) but significantly reduced NF-κB activation by inhibiting phosphorylation and proteolytic cleavage of the inhibitory subunit IκBα. The data indicate an important role of mitochondrial reactive oxygen species in regulation of the NF-κB pathway and corresponding age-related inflammatory activation of endothelium. Impact Journals LLC 2014-08-13 /pmc/articles/PMC4169860/ /pubmed/25239871 Text en Copyright: © 2014 Zinovkin et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zinovkin, Roman A. Romaschenko, Valeria P. Galkin, Ivan I. Zakharova, Vlada V. Pletjushkina, Olga Yu. Chernyak, Boris V. Popova, Ekaterina N.
spellingShingle	Zinovkin, Roman A. Romaschenko, Valeria P. Galkin, Ivan I. Zakharova, Vlada V. Pletjushkina, Olga Yu. Chernyak, Boris V. Popova, Ekaterina N. Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium
author_facet	Zinovkin, Roman A. Romaschenko, Valeria P. Galkin, Ivan I. Zakharova, Vlada V. Pletjushkina, Olga Yu. Chernyak, Boris V. Popova, Ekaterina N.
author_sort	Zinovkin, Roman A.
title	Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium
title_short	Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium
title_full	Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium
title_fullStr	Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium
title_full_unstemmed	Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium
title_sort	role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium
description	Vascular aging is accompanied by increases in circulatory proinflammatory cytokines leading to inflammatory endothelial response implicated in early atherogenesis. To study the possible role of mitochondria-derived reactive oxygen species (ROS) in this phenomenon, we applied the effective mitochondria-targeted antioxidant SkQ1, the conjugate of plastoquinone with dodecyltriphenylphosphonium. Eight months treatment of (CBAxC57BL/6) F1 mice with SkQ1 did not prevent age-related elevation of the major proinflammatory cytokines TNF and IL-6 in serum, but completely abrogated the increase in adhesion molecule ICAM1 expression in aortas of 24-month-old animals. In endothelial cell culture, SkQ1 also attenuated TNF-induced increase in ICAM1, VCAM, and E-selectin expression and secretion of IL-6 and IL-8, and prevented neutrophil adhesion to the endothelial monolayer. Using specific inhibitors to transcription factor NF-κB and stress-kinases p38 and JNK, we demonstrated that TNF-induced ICAM1 expression depends mainly on NF-κB activity and, to a lesser extent, on p38. SkQ1 had no effect on p38 phosphorylation (activation) but significantly reduced NF-κB activation by inhibiting phosphorylation and proteolytic cleavage of the inhibitory subunit IκBα. The data indicate an important role of mitochondrial reactive oxygen species in regulation of the NF-κB pathway and corresponding age-related inflammatory activation of endothelium.
publisher	Impact Journals LLC
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169860/
_version_	1613135767772594176

Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium

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