Mitochondria-targeted antioxidants prevent TNFα-induced endothelial cell damage

被引：24

作者：

Galkin, I. I. ^{[1
,2
]}

Pletjushkina, O. Yu ^{[1
,3
]}

Zinovkin, R. A. ^{[2
,3
]}

Zakharova, V. V. ^{[3
,4
]}

Birjukov, I. S. ^{[4
]}

Chernyak, B. V. ^{[1
,3
]}

Popova, E. N. ^{[1
,3
]}

机构：

[1] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia

[2] Moscow MV Lomonosov State Univ, Biol Fac, Moscow 119991, Russia

[3] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119991, Russia

[4] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia

来源：

BIOCHEMISTRY-MOSCOW | 2014年 / 79卷 / 02期

基金：

俄罗斯基础研究基金会;

关键词：

endothelium; apoptosis; mitochondria-targeted antioxidant; inflammation; TNF alpha; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; CYTOCHROME-C; PLASTOQUINONE DERIVATIVES; INTERRUPT EXECUTION; OXIDATIVE STRESS; APOPTOSIS; ACTIVATION; MEMBRANE; RELEASE;

D O I：

10.1134/S0006297914020059

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Increased serum level of tumor necrosis factor alpha (TNF alpha) causes endothelial dysfunction and leads to serious vascular pathologies. TNF alpha signaling is known to involve reactive oxygen species (ROS). Using mitochondria-targeted antioxidant SkQR1, we studied the role of mitochondrial ROS in TNF alpha-induced apoptosis of human endothelial cell line EAhy926. We found that 0.2 nM SkQR1 prevents TNF alpha-induced apoptosis. SkQR1 has no influence on TNF alpha-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 TNF alpha-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 TNF alpha-initiated endothelial cell death, and they suggest the potential of mitochondria-targeted antioxidants as vasoprotectors.

引用

页码：124 / 130

页数：7

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