Poly(ADP-ribose) polymerase inhibition prevents reactive oxygen species induced inhibition of aldehyde dehydrogenase2 activity

Shu-jian Wei; Jun-hui Xing; Bai-lu Wang; Li Xue; Jia-li Wang; Rui Li; Wei-dong Qin; Juan Wang; Xu-ping Wang; Ming-xiang Zhang; Yu-guo Chen

doi:10.1016/j.bbamcr.2012.11.007

Poly(ADP-ribose) polymerase inhibition prevents reactive oxygen species induced inhibition of aldehyde dehydrogenase2 activity

Biochim Biophys Acta. 2013 Mar;1833(3):479-86. doi: 10.1016/j.bbamcr.2012.11.007. Epub 2012 Nov 13.

Authors

Shu-jian Wei¹, Jun-hui Xing, Bai-lu Wang, Li Xue, Jia-li Wang, Rui Li, Wei-dong Qin, Juan Wang, Xu-ping Wang, Ming-xiang Zhang, Yu-guo Chen

Affiliation

¹ The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Qilu Hospital, Jinan, Shandong, China.

PMID: 23159776
DOI: 10.1016/j.bbamcr.2012.11.007

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehyde Dehydrogenase / antagonists & inhibitors*
Aldehyde Dehydrogenase / metabolism
Aldehyde Dehydrogenase, Mitochondrial
Animals
Aorta / cytology
Aorta / drug effects
Aorta / metabolism
Blotting, Western
Cells, Cultured
Endothelium, Vascular / cytology
Endothelium, Vascular / drug effects
Endothelium, Vascular / metabolism
Enzyme Inhibitors / pharmacology
Fluorescent Antibody Technique
Humans
Immunoenzyme Techniques
Immunoprecipitation
Lipid Peroxidation / drug effects
Lipoproteins, LDL / metabolism*
Male
Myocardial Reperfusion Injury / drug therapy*
Myocardial Reperfusion Injury / metabolism
Myocardial Reperfusion Injury / pathology
Poly(ADP-ribose) Polymerase Inhibitors*
Poly(ADP-ribose) Polymerases / metabolism
RNA, Small Interfering / genetics
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism*
Reperfusion Injury / drug therapy*
Reperfusion Injury / metabolism
Reperfusion Injury / pathology
Sirtuin 3 / antagonists & inhibitors
Sirtuin 3 / genetics
Sirtuin 3 / metabolism

Substances

Enzyme Inhibitors
Lipoproteins, LDL
Poly(ADP-ribose) Polymerase Inhibitors
RNA, Small Interfering
Reactive Oxygen Species
oxidized low density lipoprotein
ALDH2 protein, human
Aldehyde Dehydrogenase
Aldehyde Dehydrogenase, Mitochondrial
Poly(ADP-ribose) Polymerases
SIRT3 protein, human
Sirtuin 3