Mitochondria-Targeted Antioxidants Prevent TNFα-Induced Endothelial Cell Damage

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I. I. Galkin^1,2*, O. Yu. Pletjushkina^1,3, R. A. Zinovkin^2,3, V. V. Zakharova^3,4, I. S. Birjukov⁴, B. V. Chernyak^1,3, and E. N. Popova^1,3

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Vorobyevy Gory 1, 119991 Moscow, Russia; fax: +7 (495) 939-0338; E-mail: galkin.ivan.i@gmail.com

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

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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.

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KEY WORDS: endothelium, apoptosis, mitochondria-targeted antioxidant, inflammation, TNFα

DOI: 10.1134/S0006297914020059

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