Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance

Reactive aldehydes can initiate protein oxidative damage which may contribute to heart senescence. Sirtuin 1 (SIRT1) is considered to be a potential interventional target for I/R injury management in the elderly. We hypothesized that aldehyde mediated carbonyl stress increases susceptibility of aged...

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Bibliographic Details
Published in:PloS one 2013-09, Vol.8 (9), p.e74050
Main Authors: Gu, Chunhu, Xing, Yuan, Jiang, Li, Chen, Mai, Xu, Ming, Yin, Yue, Li, Chen, Yang, Zheng, Yu, Lu, Ma, Heng
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Age
Age Factors
Aging
Aging - metabolism
Aldehyde dehydrogenase
Aldehyde Dehydrogenase - metabolism
Aldehyde Dehydrogenase, Mitochondrial
Aldehydes
Aldehydes - adverse effects
Animals
Benzamides - administration & dosage
Benzodioxoles - administration & dosage
Biocompatibility
Carbonyl compounds
Carbonyls
Cardiomyocytes
Cell cycle
Data processing
Dehydrogenases
Disease Models, Animal
Enzyme Activation
Enzymes
Geriatrics
Heart
Heart diseases
Hospitals
House mouse
Hypoxia
Injuries
Intolerance
Ischemia
Laboratory animals
Male
Metabolism
Mice
Mice, Knockout
Muscle contraction
Myocardial Ischemia - metabolism
Myocardial Ischemia - physiopathology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - physiopathology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Older people
Oxidative stress
Physiology
Proteins
Reperfusion
Rodents
Senescence
SIRT1 protein
Sirtuin 1 - metabolism
Stress, Physiological - drug effects
Stresses
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Summary:Reactive aldehydes can initiate protein oxidative damage which may contribute to heart senescence. Sirtuin 1 (SIRT1) is considered to be a potential interventional target for I/R injury management in the elderly. We hypothesized that aldehyde mediated carbonyl stress increases susceptibility of aged hearts to ischemia/reperfusion (I/R) injury, and elucidate the underlying mechanisms with a focus on SIRT1. Male C57BL/6 young (4-6 mo) and aged (22-24 mo) mice were subjected to myocardial I/R. Cardiac aldehyde dehydrogenase (ALDH2), SIRT1 activity and protein carbonyls were assessed. Our data revealed that aged heart exhibited increased endogenous aldehyde/carbonyl stress due to impaired ALDH2 activity concomitant with blunted SIRT1 activity (P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0074050