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Mitochondria-targeted antioxidants prevent TNFα induced endothelial cell damageтезисы доклада
- Авторы: Zakharova V.V., Galkin I.I., Pletjushkina O.Y., Chernyak B.V., Zinovkin R.A., Popova E.N.
- Сборник: Abstract Book
- Серия: 21st ECDO Euroconference on Apoptosis and 10th Training course on "Concepts and Methods in Programmed Cell Death", Paris-France, September 25-28
- Тезисы
- Год издания: 2013
- Первая страница: 109
- Последняя страница: 109
- Аннотация: Using mitochondria-targeted antioxidants (SkQs), we tested the role of mitochondrial reactive oxygen species (ROS) in the TNFα-induced apoptosis and cytoskeleton reorganization of endothelial cells. TNFα induced apoptosis in endothelial cells line EAhy926. SkQs, as well as the classic antioxidant N-acetylcysteine and Trolox significantly reduced apoptotic action of TNFα. SkQs had no effect on TNFα-dependent proteolytic activation of the initiator caspase-8 and proteolysis of its substrate protein Bid, but inhibited Bid-dependent cytochrome c release, and subsequent cleavage of caspase-3 and its substrate PARP. Previously it had been shown on isolated mitochondria that SkQs prevents the oxidation of cardiolipin caused by oxidative stress [Skulachev VP et al. 2009]. In turn, oxidation of cardiolipin leads to cytochrome c release [Ott M et al. 2007]. Mitochondrial membrane permeabilization (MMP) is required to release of proapoptotic proteins out from the intermembrane space is regulated by Bcl-2 proteins [Kroemer G et al. 2007]. We found that SkQs treatment increased level of protein Bcl-2 and decreased levels of Bax and p53. TNFα at non-toxic concentrations (up to 5 ng/ml) induced substantial cytoskeleton restructuring in endothelial cells: disassembly of peripheral ring of actin and associated intercellular contacts as well as stress fibers formation. Cytoskeleton rearrangement was accompanied by retardation of directional movement of cells in the in vitro scratch assay. SkQs pretreatment prevented disassembly of peripheral ring of actin, release of VE-cadherin from cell-cell contacts and its proteolysis, but had no effect on the formation of stress fibrils and cell migration to the "wound". But SkQs alone increased speed of cell migration to the "wound". Thus, it was shown that mitochondrial ROS in the endothelial cell line EAhy926 keep up initiated TNFα signals of apoptosis and disintegration of the cell monolayer. At the same time, mitochondrial ROS seemed indispensable for the signaling events leading to stress fibers formation and suppression of cell motility in the wound closure.
- Добавил в систему: Захарова Влада Вячеславовна