Abstract
Lipid peroxidation plays a critical role in cardiovascular diseases. Aldehydes are the major end products of lipid peroxidation and can be metabolized into less reactive chemical species by aldehyde dehydrogenase 2 (ALDH2). However, ALDH2 dehydrogenase activity can be affected by many factors including reactive oxygen species. To elucidate how reactive oxygen species inhibit ALDH2 dehydrogenase activity, we stimulated human aortic endothelial cells (HAECs) with oxidized low-density lipoproteins (ox-LDL) and performed a myocardial ischemia-reperfusion model. Ox-LDL treatment and ischemia-reperfusion injury inhibited ALDH2 dehydrogenase activity. Poly(ADP-ribose) polymerase (PARP) was activated by ox-LDL stimulation and ischemia-reperfusion injury and PARP inhibition partly restored ALDH2 dehydrogenase activity in ox-LDL treated HAECs and ischemia-reperfusion rat hearts. SIRT3 was upregulated by ox-LDL stimulation and ischemia-reperfusion injury and downregulated by PARP inhibition. Using siRNA to knock down SIRT3, we demonstrated that SIRT3 mediated deacetylation decreased ALDH2 dehydrogenase activity and PARP inhibition partly restored ALDH2 dehydrogenase activity through preventing SIRT3 expression and subsequently preserving ALDH2 acetylation.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Dehydrogenase / antagonists & inhibitors*
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Aldehyde Dehydrogenase / metabolism
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Aldehyde Dehydrogenase, Mitochondrial
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Animals
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Aorta / cytology
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Aorta / drug effects
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Aorta / metabolism
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Blotting, Western
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Cells, Cultured
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism
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Enzyme Inhibitors / pharmacology
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Fluorescent Antibody Technique
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Humans
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Immunoenzyme Techniques
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Immunoprecipitation
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Lipid Peroxidation / drug effects
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Lipoproteins, LDL / metabolism*
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Male
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Myocardial Reperfusion Injury / drug therapy*
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Myocardial Reperfusion Injury / metabolism
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Myocardial Reperfusion Injury / pathology
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Poly(ADP-ribose) Polymerase Inhibitors*
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Poly(ADP-ribose) Polymerases / metabolism
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RNA, Small Interfering / genetics
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Rats
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Rats, Wistar
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Reactive Oxygen Species / metabolism*
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Reperfusion Injury / drug therapy*
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Reperfusion Injury / metabolism
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Reperfusion Injury / pathology
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Sirtuin 3 / antagonists & inhibitors
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Sirtuin 3 / genetics
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Sirtuin 3 / metabolism
Substances
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Enzyme Inhibitors
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Lipoproteins, LDL
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Poly(ADP-ribose) Polymerase Inhibitors
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RNA, Small Interfering
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Reactive Oxygen Species
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oxidized low density lipoprotein
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ALDH2 protein, human
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Aldehyde Dehydrogenase
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Aldehyde Dehydrogenase, Mitochondrial
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Poly(ADP-ribose) Polymerases
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SIRT3 protein, human
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Sirtuin 3