ИСТИНА

In endothelial cells TNFa activates secretion of blood coagulation factors, NO-synthase, expression of tissue factors, adhesion molecules, inflammatory cytokines and chemokines, transendothelial vesicular transport, cytoskeleton reorganization, disassembly of cell–cell contacts, and cell death [1]. The increased serum level of tumor necrosis factor-a (TNFa) causes endothelial dysfunction and leads to serious vascular pathologies. The TNFa signaling is known to involve reactive oxygen species. Using mitochondria-targeted antioxidant SkQR1, we have studied the role of mitochondrial reactive oxygen species in TNFa-induced apoptosis of human endothelial cell line EAhy926. It is found that 0.2 nM SkQR1 prevents TNFa-induced apoptosis, but has no influence on TNFa-dependent proteolytic activation of caspase-8 and Bid, inhibits cytochrome c release from mitochondria and cleavage of caspase-3 and PARP. The SkQ-derived compounds lacking the antioxidant moieties do not prevent TNFainduced apoptosis. The antiapoptotic action of SkQR1 may also be related to other observations made in these experiments, namely SkQR1-induced increase in Bcl-2 and corresponding decrease in Bax as well as p53. The results indicate mitochondrial reactive oxygen species production is involved in TNFa-initiated endothelial cell death, and implies potential of the mitochondria-targeted antioxidants as vasoprotectors. Probably the vasoprotective action of SkQ1 and SkQR1 explains the therapeutic effect of these compounds observed in renal and brain failure animal models [2,3].