ALDH-2 deficiency increases cardiovascular oxidative stress--evidence for indirect antioxidative properties.

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RESEARCH PRODUCT

ALDH-2 deficiency increases cardiovascular oxidative stress--evidence for indirect antioxidative properties.

Andrea Pautz Sarah Zurmeyer Swenja Schuhmacher Leszek Wojnowski Philip Wenzel Andreas Daiber Eberhard Schulz Toshihiro Kawamoto Hartmut Kleinert Johanna Müller Thomas Münzel Matthias Oelze

subject

Mitochondrial ROS Antioxidant medicine.medical_treatment Biophysics Aldehyde dehydrogenase Acetaldehyde Mitochondrion Pharmacology medicine.disease_cause Biochemistry Cardiovascular System Models Biological Antioxidants chemistry.chemical_compound Mice Nitroglycerin medicine Animals Humans Cysteine Molecular Biology chemistry.chemical_classification Reactive oxygen species biology Dose-Response Relationship Drug Aldehyde Dehydrogenase Mitochondrial Acetaldehyde Cell Biology Glutathione Aldehyde Dehydrogenase Glutathione Mitochondria Mice Inbred C57BL Dithiothreitol Oxidative Stress chemistry Biochemistry Doxorubicin cardiovascular system biology.protein Reactive Oxygen Species Oxidative stress

description

Abstract 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 C57Bl6 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 C57Bl6 mice. Our results suggest that ALDH-2 has an indirect antioxidative property independent of its thiol-moiety in disease states of cardiovascular oxidative stress.

year	journal	country	edition	language
2007-11-27	Biochemical and biophysical research communications

10.1016/j.bbrc.2007.12.089 https://pubmed.ncbi.nlm.nih.gov/18157936