title: Mitochondria-targeted antioxidants prevent TNFα-induced endothelial cell damage.
abstract: 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.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia. galkin.ivan.i@gmail.com.
authors.forename: I I
authors.initials: II
authors.lastname: Galkin
authors.forename: O Yu
authors.initials: OY
authors.lastname: Pletjushkina
authors.forename: R A
authors.initials: RA
authors.lastname: Zinovkin
authors.forename: V V
authors.initials: VV
authors.lastname: Zakharova
authors.forename: I S
authors.initials: IS
authors.lastname: Birjukov
authors.forename: B V
authors.initials: BV
authors.lastname: Chernyak
authors.forename: E N
authors.initials: EN
authors.lastname: Popova
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D012235:Rhodamines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C534903:10-(6'-plastoquinonyl) decylrhodamine 19; C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D012235:Rhodamines; D014409:Tumor Necrosis Factor-alpha; D010971:Plastoquinone