| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received March 10, 2006
Revised April 10, 2006
Accepted after revision May 8, 2006
1 University of Alberta
* To whom correspondence should be addressed. E-mail: gary.lopaschuk{at}ualberta.ca.
AMP-activated protein kinase (AMPK) has emerged as a key regulator of energy metabolism in the heart. The high energy demands of the heart are primarily met by the metabolism of both fatty acids and glucose, both processes being regulated by AMPK. During myocardial ischemia a rapid activation of AMPK occurs, resulting in an activation of both glucose uptake and glycolysis, as well as an increase in fatty acid oxidation. This activation of AMPK has the potential to increase energy production and to inhibit apoptosis, thereby protecting the heart during the ischemic stress. However, at clinically relevant high levels of fatty acids, ischemic- induced activation of AMPK also stimulates fatty acid oxidation during and following ischemia. This can contribute to ischemic injury secondary to an inhibition of glucose oxidation, which results in a decrease in cardiac efficiency. In a number of other non-cardiac tissues, AMPK has been shown to have pro-apoptotic effects. As a result, the question of whether AMPK activation benefits or harms the ischemic heart remains controversial. The role of AMPK in cardiac hypertrophy is also controversial. Activation of AMPK inhibits protein synthesis, and may be an adaptive response to pathological cardiac hypertrophy. However, both activating and inactivating mutations of AMPK in mice are associated with a marked cardiac hypertrophy. This review will address the issue of whether AMPK activation acts as an enemy or ally to the ischemic and hypertrophied heart. Resolving this issue has important implications as to whether therapeutic approaches to protect the ischemic heart should be developed which either activate or inhibit AMPK.
This article has been cited by other articles:
|
|
 |
|
  L. Bertrand, S. Horman, C. Beauloye, and J.-L. Vanoverschelde Insulin signalling in the heart Cardiovasc Res, July 15, 2008; 79(2): 238 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Ussher and G. D. Lopaschuk The malonyl CoA axis as a potential target for treating ischaemic heart disease Cardiovasc Res, July 15, 2008; 79(2): 259 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Doenst, H. Bugger, M. Schwarzer, G. Faerber, M. A. Borger, and F. W. Mohr Three good reasons for heart surgeons to understand cardiac metabolism Eur. J. Cardiothorac. Surg., May 1, 2008; 33(5): 862 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Calvert, S. Gundewar, S. Jha, J. J.M. Greer, W. H. Bestermann, R. Tian, and D. J. Lefer Acute Metformin Therapy Confers Cardioprotection Against Myocardial Infarction Via AMPK-eNOS-Mediated Signaling Diabetes, March 1, 2008; 57(3): 696 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Omar, H. Fraser, and A. S. Clanachan Ischemia-induced activation of AMPK does not increase glucose uptake in glycogen-replete isolated working rat hearts Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1266 - H1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Kim, J.-T. Hwang, H. Yun, S.-G. Chi, S.-J. Lee, I. Kang, K.-S. Yoon, W.-J. Choe, S.-S. Kim, and J. Ha Inhibition of AMP-activated Protein Kinase Sensitizes Cancer Cells to Cisplatin-induced Apoptosis via Hyper-induction of p53 J. Biol. Chem., February 15, 2008; 283(7): 3731 - 3742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Young AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra Circulation, February 12, 2008; 117(6): 832 - 840. [Full Text] [PDF]
|
|
|
|
|
|
L. Zhou, H. Huang, C. L. Yuan, W. Keung, G. D. Lopaschuk, and W. C. Stanley Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H954 - H960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Gollob Modulating Phenotypic Expression of the PRKAG2 Cardiac Syndrome Circulation, January 15, 2008; 117(2): 134 - 135. [Full Text] [PDF]
|
|
|
|
|
|
J. R.B. Dyck The Ischemic Heart: Starving to Stimulate the Adiponectin-AMPK Signaling Axis Circulation, December 11, 2007; 116(24): 2779 - 2781. [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura, K. Tamaki, K. Saito, Y. Nakano, T. Tobe, and R. Bolli Cardioprotective Effects of Short-Term Caloric Restriction Are Mediated by Adiponectin via Activation of AMP-Activated Protein Kinase Circulation, December 11, 2007; 116(24): 2809 - 2817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Berthiaume, M. Laplante, W. T. Festuccia, K. Cianflone, L. P. Turcotte, D. R. Joanisse, G. Olivecrona, R. Thieringer, and Y. Deshaies 11beta-HSD1 inhibition improves triglyceridemia through reduced liver VLDL secretion and partitions lipids toward oxidative tissues Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1045 - E1052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Kim, S.-N. Jung, K. H. Son, S. R. Kim, T. Y. Ha, M. G. Park, I. G. Jo, J. G. Park, W. Choe, S.-S. Kim, et al. Antidiabetes and Antiobesity Effect of Cryptotanshinone via Activation of AMP-Activated Protein Kinase Mol. Pharmacol., July 1, 2007; 72(1): 62 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, H. He, and J. A. Balschi Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H457 - H466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Carvajal, E. Zarrinpashneh, O. Szarszoi, F. Joubert, Y. Athea, P. Mateo, B. Gillet, S. Vaulont, B. Viollet, X. Bigard, et al. Dual cardiac contractile effects of the {alpha}2-AMPK deletion in low-flow ischemia and reperfusion Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3136 - H3147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Arad, C. E. Seidman, and J.G. Seidman AMP-Activated Protein Kinase in the Heart: Role During Health and Disease Circ. Res., March 2, 2007; 100(4): 474 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Saks, R. Favier, R. Guzun, U. Schlattner, and T. Wallimann Molecular system bioenergetics: regulation of substrate supply in response to heart energy demands J. Physiol., December 15, 2006; 577(3): 769 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. W. Dolinsky and J. R. B. Dyck Role of AMP-activated protein kinase in healthy and diseased hearts Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2557 - H2569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xie, D. Zhang, J. R. B. Dyck, Y. Li, H. Zhang, M. Morishima, D. L. Mann, G. E. Taffet, A. Baldini, D. S. Khoury, et al. A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway PNAS, November 14, 2006; 103(46): 17378 - 17383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kumar and C. Peers AMP-activated protein kinase: function and dysfunction in health and disease J. Physiol., July 1, 2006; 574(1): 3 - 6. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
