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

Zinovkin, R.A.; Romaschenko, V.P.; Galkin, I.I.; Zakharova, V.V.; Pletjushkina, O.Y.; Chernyak, B.V.; Popova, E.N.

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Web of Science, Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 27 мая 2015 г.

Авторы: Zinovkin Roman A., Romaschenko Valeria P., Galkin Ivan I., Zakharova Vlada V., Pletjushkina Olga Yu, Chernyak Boris V., Popova Ekaterina N.
Журнал: AGING-US
Том: 6
Номер: 8
Год издания: 2014
Первая страница: 661
Последняя страница: 674
DOI: 10.18632/aging.100685
Аннотация: 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-kappaB and stress-kinases p38 and JNK, we demonstrated that TNF-induced ICAM1 expression depends mainly on NF-kappaB activity and, to a lesser extent, on p38. SkQ1 had no effect on p38 phosphorylation (activation) but significantly reduced NF-kappaB activation by inhibiting phosphorylation and proteolytic cleavage of the inhibitory subunit IkappaBalpha. The data indicate an important role of mitochondrial reactive oxygen species in regulation of the NF-kappaB pathway and corresponding age-related inflammatory activation of endothelium.
Добавил в систему: Зиновкин Роман Алексеевич

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

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