2Biological Faculty, Lomonosov Moscow State University, Vorobyevy Gory 1, 119991 Moscow, Russia
3Institute of Mitoengineering, Lomonosov Moscow State University, Vorobyevy Gory 1, 119991 Moscow, Russia
4Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Vorobyevy Gory 1, 119991 Moscow, Russia
* To whom correspondence should be addressed.
Received September 24, 2013; Revision received October 23, 2013
Increased serum level of tumor necrosis factor α (TNFα) causes endothelial dysfunction and leads to serious vascular pathologies. TNFα signaling is known to involve reactive oxygen species (ROS). Using mitochondria-targeted antioxidant SkQR1, we studied the role of mitochondrial ROS in TNFα-induced apoptosis of human endothelial cell line EAhy926. We found that 0.2 nM SkQR1 prevents TNFα-induced apoptosis. SkQR1 has no influence on TNFα-dependent proteolytic activation of caspase-8 and Bid, but it inhibits cytochrome c release from mitochondria and cleavage of caspase-3 and its substrate PARP. SkQ analogs lacking the antioxidant moieties do not prevent TNFα-induced apoptosis. The antiapoptotic action of SkQR1 may 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. These results indicate that mitochondrial ROS production is involved in TNFα-initiated endothelial cell death, and they suggest the potential of mitochondria-targeted antioxidants as vasoprotectors.
KEY WORDS: endothelium, apoptosis, mitochondria-targeted antioxidant, inflammation, TNFα