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(2009)
J Mol Cell Cardiol
L. Valentim, K. Laurence, P. Townsend, C. Carroll, S. Soond, T. Scarabelli, R. Knight, D. Latchman, A. Stephanou (2006)
Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury.Journal of molecular and cellular cardiology, 40 6
Y. Matsui, S. Kyoi, H. Takagi, Chiao-Po Hsu, N. Hariharan, T. Ago, S. Vatner, J. Sadoshima (2008)
Molecular mechanisms and physiological significance of autophagy during myocardial ischemia and reperfusionAutophagy, 4
S. Goswami, D. Das (2006)
Autophagy in the myocardium: Dying for survival?Experimental and clinical cardiology, 11 3
H. Mehenni, N. Lin-Marq, K. Buchet-Poyau, A. Reymond, M. Collart, D. Picard, S. Antonarakis (2005)
LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes.Human molecular genetics, 14 15
K. Inoki, Tianqing Zhu, K. Guan (2003)
TSC2 Mediates Cellular Energy Response to Control Cell Growth and SurvivalCell, 115
D. Hickson-Bick, Chad Jones, L. Buja (2008)
Stimulation of mitochondrial biogenesis and autophagy by lipopolysaccharide in the neonatal rat cardiomyocyte protects against programmed cell death.Journal of molecular and cellular cardiology, 44 2
S. Khan, F. Salloum, Anindita Das, Lei Xi, G. Vetrovec, R. Kukreja (2006)
Rapamycin confers preconditioning-like protection against ischemia-reperfusion injury in isolated mouse heart and cardiomyocytes.Journal of molecular and cellular cardiology, 41 2
A. Renner, Martina Sagstetter, H. Harms, V. Lange, M. Götz, O. Elert (2005)
Formation of 4-hydroxy-2-nonenal protein adducts in the ischemic rat heart after transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 24 6
Shi‐Yan Li, Jun Ren (2008)
Cardiac overexpression of alcohol dehydrogenase exacerbates chronic ethanol ingestion-induced myocardial dysfunction and hypertrophy: role of insulin signaling and ER stress.Journal of molecular and cellular cardiology, 44 6
Proc Natl Acad Sci USA, 96
E. Churchill, M. Disatnik, D. Mochly‐Rosen (2009)
Time-dependent and ethanol-induced cardiac protection from ischemia mediated by mitochondrial translocation of varepsilonPKC and activation of aldehyde dehydrogenase 2.Journal of molecular and cellular cardiology, 46 2
M. Mocanu, D. Yellon (2007)
PTEN, the Achilles' heel of myocardial ischaemia/reperfusion injury?British Journal of Pharmacology, 150
N. Karia, D. Adlam, R. Dhunnookchand, N. Sabharwal (2011)
Three-dimensional transoesophageal echocardiography of an aberrant chordae tendinae causing aortic valvular regurgitation.European heart journal, 32 8
R. Russell, Ji Li, David Coven, M. Pypaert, C. Zechner, M. Palmeri, F. Giordano, J. Mu, M. Birnbaum, L. Young (2004)
AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury.The Journal of clinical investigation, 114 4
R. Decher, A. Poole, J. Dingle, K. Wildenthal (1978)
Influence of methylprednisolone of the sequential redistribution of cathepsin D and other lysosomal enzymes during myocardial ischemia in rabbits.The Journal of clinical investigation, 62 4
Å. Gustafsson, R. Gottlieb (2009)
Autophagy in Ischemic Heart DiseaseCirculation Research, 104
A. Clerk, S. Cole, T. Cullingford, J. Harrison, M. Jormakka, D. Valks (2003)
Regulation of cardiac myocyte cell death.Pharmacology & therapeutics, 97 3
V. Dolinsky, Anita Chan, I. Frayne, P. Light, C. Rosiers, J. Dyck (2009)
Resveratrol Prevents the Prohypertrophic Effects of Oxidative Stress on LKB1Circulation, 119
Atsuko Nakai, O. Yamaguchi, T. Takeda, Y. Higuchi, S. Hikoso, M. Taniike, S. Omiya, Isamu Mizote, Y. Matsumura, M. Asahi, K. Nishida, M. Hori, N. Mizushima, K. Otsu (2007)
The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stressNature Medicine, 13
W. Liu, A. Akhand, K. Takeda, Y. Kawamoto, M. Itoigawa, M. Kato, H. Suzuki, N. Ishikawa, I. Nakashima (2003)
Protein phosphatase 2A-linked and -unlinked caspase-dependent pathways for downregulation of Akt kinase triggered by 4-hydroxynonenalCell Death and Differentiation, 10
Jun Ren (2007)
Acetaldehyde and alcoholic cardiomyopathy: lessons from the ADH and ALDH2 transgenic models.Novartis Foundation symposium, 285
J. Qian, Xiaoping Ren, Xiaohong Wang, Pengyuan Zhang, W. Jones, J. Molkentin, G. Fan, E. Kranias, G. F (2009)
Blockade of Hsp20 Phosphorylation Exacerbates Cardiac Ischemia/Reperfusion Injury by Suppressed Autophagy and Increased Cell DeathCirculation Research, 105
A. Hamacher-Brady, N. Brady, R. Gottlieb (2006)
Enhancing Macroautophagy Protects against Ischemia/Reperfusion Injury in Cardiac Myocytes*Journal of Biological Chemistry, 281
S. Arico, A. Petiot, C. Bauvy, P. Dubbelhuis, A. Meijer, P. Codogno, E. Ogier-Denis (2001)
The Tumor Suppressor PTEN Positively Regulates Macroautophagy by Inhibiting the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway*The Journal of Biological Chemistry, 276
Che-Hong Chen, G. Budas, E. Churchill, M. Disatnik, T. Hurley, D. Mochly‐Rosen (2008)
Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the HeartScience, 321
M. Arad, C. Seidman, J. Seidman (2007)
AMP-Activated Protein Kinase in the Heart: Role During Health and DiseaseCirculation Research, 100
P. Usatyuk, N. Parinandi, V. Natarajan (2006)
Redox Regulation of 4-Hydroxy-2-nonenal-mediated Endothelial Barrier Dysfunction by Focal Adhesion, Adherens, and Tight Junction Proteins*Journal of Biological Chemistry, 281
E. Miller, Ji Li, L. Leng, Courtney McDonald, T. Atsumi, R. Bucala, L. Young (2008)
Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heartNature, 451
Shi‐Yan Li, Qun Li, J. Shen, F. Dong, V. Sigmon, Yizhen Liu, Jun Ren (2006)
Attenuation of acetaldehyde-induced cell injury by overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene in human cardiac myocytes: role of MAP kinase signaling.Journal of molecular and cellular cardiology, 40 2
K. Inoki, Yong Li, Tian Zhu, Jun Wu, K. Guan (2002)
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signallingNature Cell Biology, 4
Y. Matsui, H. Takagi, X. Qu, M. Abdellatif, H. Sakoda, T. Asano, B. Levine, J. Sadoshima (2007)
Distinct Roles of Autophagy in the Heart During Ischemia and Reperfusion: Roles of AMP-Activated Protein Kinase and Beclin 1 in Mediating AutophagyCirculation Research, 100
A. Halapas, A. Armakolas, M. Koutsilieris (2008)
Autophagy: a target for therapeutic interventions in myocardial pathophysiology.Expert opinion on therapeutic targets, 12 12
T. Doser, S. Turdi, D. Thomas, P. Epstein, Shi‐Yan Li, Jun Ren (2009)
Transgenic Overexpression of Aldehyde Dehydrogenase-2 Rescues Chronic Alcohol Intake–Induced Myocardial Hypertrophy and Contractile DysfunctionCirculation, 119
Qun Li, Xiaoping Yang, N. Sreejayan, Jun Ren (2007)
Insulin-like growth factor I deficiency prolongs survival and antagonizes paraquat-induced cardiomyocyte dysfunction: role of oxidative stress.Rejuvenation research, 10 4
G. Oudit, Hui Sun, B. Kerfant, M. Crackower, J. Penninger, P. Backx (2004)
The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease.Journal of molecular and cellular cardiology, 37 2
A. Kraaij, H. Jonge, H. Esterbauer, J. Vente, H. Steinbusch, J. Koster (1990)
Cumene hydroperoxide, an agent inducing lipid peroxidation, and 4-hydroxy-2,3-nonenal, a peroxidation product, cause coronary vasodilatation in perfused rat hearts by a cyclic nucleotide independent mechanism.Cardiovascular research, 24 2
D. Lucas, L. Szweda (1999)
Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-ketoglutarate dehydrogenase.Proceedings of the National Academy of Sciences of the United States of America, 96 12
Yiping Gu, Chunjie Wang, A. Cohen (2004)
Effect of IGF‐1 on the balance between autophagy of dysfunctional mitochondria and apoptosisFEBS Letters, 577
G. Meyer, W. Martinet (2009)
Autophagy in the cardiovascular system.Biochimica et biophysica acta, 1793 9
A. Daiber, P. Wenzel, M. Oelze, T. Münzel (2007)
New insights into bioactivation of organic nitrates, nitrate tolerance and cross-toleranceClinical Research in Cardiology, 97
T. Ishikawa, H. Esterbauer, H. Sies (1986)
Role of cardiac glutathione transferase and of the glutathione S-conjugate export system in biotransformation of 4-hydroxynonenal in the heart.The Journal of biological chemistry, 261 4
M. Araki, K. Motojima (2008)
Hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma cells.Biochemical and biophysical research communications, 367 2
G. Takemura, R. Maruyama, Kazuko Goto, H. Kanamori, A. Tsujimoto, S. Minatoguchi, H. Fujiwara (2009)
Fate of isolated adult cardiomyocytes undergoing starvation-induced autophagic degenerationAutophagy, 5
N. Aberle, M. Picklo, V. Amarnath, Jun Ren (2007)
Inhibition of cardiac myocyte contraction by 4-hydroxy-trans-2-nonenalCardiovascular Toxicology, 4
P. Eaton, Jian-Mei Li, D. Hearse, M. Shattock (1999)
Formation of 4-hydroxy-2-nonenal-modified proteins in ischemic rat heart.American journal of physiology. Heart and circulatory physiology, 276 3
N. Gurusamy, István Lekli, N. Gorbunov, M. Gherghiceanu, L. Popescu, D. Das (2008)
Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 proteinJournal of Cellular and Molecular Medicine, 13
Juanjuan Chen, G. Henderson, G. Freeman (2001)
Role of 4-hydroxynonenal in modification of cytochrome c oxidase in ischemia/reperfused rat heart.Journal of molecular and cellular cardiology, 33 11
Sovan Sarkar, B. Ravikumar, RA Floto, D. Rubinsztein (2009)
Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathiesCell Death and Differentiation, 16
AimsThe present study was designed to examine the mechanism involved in mitochondrial aldehyde dehydrogenase (ALDH2)-induced cardioprotection against ischaemia/reperfusion (I/R) injury with a focus on autophagy.MethodsWild-type (WT), ALDH2 overexpression, and knockout (KO) mice (n = 4–6 for each index measured) were subjected to I/R, and myocardial function was assessed using echocardiographic, Langendroff, and edge-detection systems. Western blotting was used to evaluate AMP-dependent protein kinase (AMPK), Akt, autophagy, and the AMPK/Akt upstream signalling LKB1 and PTEN.ResultsALDH2 overexpression and KO significantly attenuated and accentuated, respectively, infarct size, factional shortening, and recovery of post-ischaemic left ventricular function following I/R as well as hypoxia/reoxygenation-induced cardiomyocyte contractile dysfunction. Autophagy was induced during ischaemia and remained elevated during reperfusion. ALDH2 significantly promoted autophagy during ischaemia, which was accompanied by AMPK activation and mammalian target of rapamycin (mTOR) inhibition. On the contrary, ALDH2 overtly inhibited autophagy during reperfusion accompanied by the activation of Akt and mTOR. Inhibition and induction of autophagy mitigated ALDH2-induced protection against cell death in hypoxia and reoxygenation, respectively. In addition, levels of the endogenous toxic aldehyde 4-hydroxy-2-nonenal (4-HNE) were elevated by ischaemia and reperfusion, which was abrogated by ALDH2. Furthermore, ALDH2 ablated 4-HNE-induced cardiomyocyte dysfunction and protein damage, whereas 4-HNE directly decreased pan and phosphorylated LKB1 and PTEN expression.ConclusionOur data suggest a myocardial protective effect of ALDH2 against I/R injury possibly through detoxification of toxic aldehyde and a differential regulation of autophagy through AMPK- and Akt-mTOR signalling during ischaemia and reperfusion, respectively.
European Heart Journal – Oxford University Press
Published: Apr 12, 2011
Keywords: ALDH2 Myocardial ischaemia/reperfusion Akt AMPK Autophagy 4-HNE
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