ALDH-2 deficiency increases cardiovascular oxidative stress -: Evidence for indirect antioxidative properties

被引：73

作者：

Wenzel, Philip ^{[1
]}

Mueller, Johanna ^{[1
]}

Zurmeyer, Sarah ^{[1
]}

Schuhmacher, Swenja ^{[1
]}

Schulz, Eberhard ^{[1
]}

Oelze, Matthias ^{[1
]}

Pautz, Andrea ^{[2
]}

Kawamoto, Toshihiro ^{[3
]}

Wojnowski, Leszek ^{[2
]}

Kleinert, Hartmut ^{[2
]}

Muenzel, Thomas ^{[1
]}

Daiber, Andreas ^{[1
]}

机构：

[1] Univ Mainz Klinikum, Med Klin 2, Lab Mol Kardiol, D-55131 Mainz, Germany

[2] Univ Mainz Klinikum, Inst Pharmakol & Toxikol, D-55101 Mainz, Germany

[3] Univ Occupat & Environm Hlth, Dept Environm Hlth, Kitakyushu, Fukuoka 8078555, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 367卷 / 01期

关键词：

mitochondrial aldehyde dehydrogenase; reactive oxygen species; vascular function; animal models of human disease;

D O I：

10.1016/j.bbrc.2007.12.089

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：

Mitochondrial aldehyde dehydrogenase (ALDH-2) reduces reactive oxygen species (ROS) formation related to toxic aldehydes; additionally, it provides a bioactivating pathway for nitroglycerin. Since acetaldehyde, nitroglycerin, and doxorubicin treatment provoke mitochondrial oxidative stress, we used ALDH-2(-/-) mice and purified recombinant human ALDH-2 to test the hypothesis that ALDH-2 has an indirect antioxidant function in mitochondria. Antioxidant capacity of purified ALDH-2 was comparable to equimolar doses of glutathione, cysteine, and dithiothreitol; mitochondrial oxidative stress was comparable in C57B16 and ALDH-2(-/-) mice after acute challenges with nitroglycerin or doxorubicin, whereas chronic acetaldehyde, nitroglycerin, and doxorubicin treatment dose-dependently increased mitochondrial ROS formation and impaired endothelial function to a greater extent in ALDH-2(-/-) mice. Maximal nitroglycerin dose applied in vivo lead to a "super-desensitized" nitroglycerin response in isolated ALDH-2(-/-) aortas, inaccessible in C57B16 mice. Our results suggest that ALDH-2 has an indirect antioxidative property independent of its thiol-moiety in disease states of cardiovascular oxidative stress. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：137 / 143

页数：7

共 33 条

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