Role of AMP-activated protein kinase in healthy and diseased hearts

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 291, Issue 6, 2006, Pages

  Dolinsky, Vernon W ^a   Dyck, Jason R B ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Cardiac energy metabolism; Cardiac hypertrophy; Glycogen; Ischemia

Indexed keywords

ADENOSINE TRIPHOSPHATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE;

ACUTE DISEASE; ADAPTATION; CARDIOMYOPATHY; CATABOLISM; CELL ENERGY; CELL FUNCTION; CELL SURVIVAL; CHRONIC DISEASE; DISEASE DURATION; DISEASE SEVERITY; ENERGY BALANCE; ENERGY CONSUMPTION; ENERGY METABOLISM; ENERGY TRANSFER; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME REGULATION; ENZYME STRUCTURE; EXERCISE; FATTY ACID OXIDATION; GLUCOSE UTILIZATION; GLYCOGEN STORAGE DISEASE; GLYCOLYSIS; HEART FUNCTION; HEART HYPERTROPHY; HEART MUSCLE CELL; HEART MUSCLE ISCHEMIA; HUMAN; INTRACELLULAR SPACE; MAMMAL; NONHUMAN; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REPERFUSION INJURY; REVIEW; STRESS; WOLFF PARKINSON WHITE SYNDROME;

ADENOSINE TRIPHOSPHATE; ANIMALS; ENERGY METABOLISM; ENZYME ACTIVATION; GLYCOLYSIS; HEART; HEART DISEASES; HUMANS; MICE; MICE, KNOCKOUT; MULTIENZYME COMPLEXES; MYOCARDIUM; PROTEIN-SERINE-THREONINE KINASES;

EID: 33845475621     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00329.2006     Document Type: Review

References (146)

1. Adams J, Chen Z, Van Denderen B, Morton C, Parker M, Witters L, Stapleton D, and Kemp B. Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site. Protein Sci 13: 155-165, 2004.
2. Allard M, Schonekess B, Henning S, English D, and Lopaschuk G. Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol Heart Circ Physiol 267: H742-H750, 1994.
3. Allard M, Wambolt R, Longnus S, Grist M, Lydell C, Parsons H, Rodrigues B, Hall J, Stanley W, and Bondy G. Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin. Am J Physiol Endocrinol Metab 279: E487-E493, 2000.
4. Altarejos J, Taniguchi M, Clanachan A, and Lopaschuk G. Myocardial ischemia differentially regulates LKB1 and an alternate 5′-AMP-activated protein kinase kinase. J Biol Chem 280: 183-190, 2005.
5. An D, Kewalramani G, Qi D, Pulinilkunnil T, Ghosh S, Abrahani A, Wambolt R, Allard M, Innis S, and Rodrigues B. β-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload. Am J Physiol Endocrinol Metab 288: E1120-E1127, 2005.
6. Arad M, Moskowitz I, Patel V, Ahmad F, Perez-Atayde A, Sawyer D, Walter M, Li G, Burgon P, Maguire C, Stapleton D, Schmitt J, Guo X, Pizard A, Kupershmidt S, Roden D, Berul C, Seidman C, and Seidman J. Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy. Circulation 107: 2850-2856, 2003.
7. Atherton P, Babraj J, Smith K, Singh J, Rennie M, and Wackerhage H. Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 19: 786-788, 2005.
8. Atkinson D. Adenine nucleotides as universal stoichiometric metabolic coupling agents. Adv Enzyme Regul 9: 207-219, 1970.
9. Awan M and Saggerson E. Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation. Biochem J 295: 61-66, 1993.
10. Baas A, Boudeau J, Sapkota G, Smit L, Medema R, Morrice N, Alessi D, and Clevers H. Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. EMBO J 22: 3062-3072, 2003.
11. Baron S, Li J, Russell R, Neumann D, Miller E, Tuerk R, Wallimann T, Hurley R, Witters L, and Young L. Dual mechanisms regulating AMPK kinase action in the ischemic heart. Circ Res 96: 337-345, 2005.
12. Beauloye C, Marsin A, Bertrand L, Vanoverschelde J, Rider M, and Hue L. The stimulation of heart glycolysis by increased workload does not require AMP-activated protein kinase but a wortmannin-sensitive mechanism. FEBS Lett 531: 324-328, 2002.
13. Bertrand L, Ginion A, Beauloye C, Hebert A, Guigas B, Hue L, and Vanoverschelde J. AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B. Am J Physiol Heart Circ Physiol 291: H239-H250, 2006.
14. Beyer A, Kitzerow A, Crute B, Kemp B, Witters L, and Heilmeyer LJ. Muscle phosphorylase kinase is not a substrate of AMP-activated protein kinase. Biol Chem 381: 457-461, 2000.
15. Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, and Watkins H. Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 10: 1215-1220, 2001.
16. Bolster D, Crozier S, Kimball S, and Jefferson L. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 277: 23977-23980, 2002.
17. Boudeau J, Baas A, Deak M, Morrice N, Kieloch A, Schutkowski M, Prescott A, Clevers H, and Alessi D. MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J 22: 5102-5114, 2003.
18. Browne G, Finn S, and Proud C. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J Biol Chem 279: 12220-12231, 2004.
19. Carling D, Aguan K, Woods A, Verhoeven A, Beri R, Brennan C, Sidebottom C, Davison M, and Scott, J. Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism. J Biol Chem 269: 11442-11448, 1994.
20. Carling D, Clarke P, Zammit V, and Hardie D. Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem 186: 129-136, 1989.
21. Carling D and Hardie D. The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase. Biochim Biophys Acta 1012: 81-86, 1989.
22. Carling D, Zammit V, and Hardie D. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett 223: 217-222, 1987.
23. Chan A, Soltys C, Young M, Proud C, and Dyck J. Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J Biol Chem 279: 32771-32779, 2004.
24. Chen Z, Heierhorst J, Mann R, Mitchelhill K, Michell B, Witters L, Lynch G, Kemp B, and Stapleton D. Expression of the AMP-activated protein kinase beta1 and beta2 subunits in skeletal muscle. FEBS Lett 460: 343-348, 1999.
25. Cheung P, Salt I, Davies S, Hardie D, and Carling D. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem J 346: 659-669, 2000.
26. Clark H, Carling D, and Saggerson D. Covalent activation of heart AMP-activated protein kinase in response to physiological concentrations of long-chain fatty acids. Eur J Biochem 271: 2215-2224, 2004.
27. Collier C, Bruce C, Smith A, Lopaschuk G, and Dyck J. Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. Am J Physiol Endocrinol Metab 291: E182-E189, 2006.
28. Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R, Zhao G, Marsh K, Kym P, Jung P, Camp H, and Frevert E. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 3: 403-416, 2006.
29. Coven D, Hu X, Cong L, Bergeron R, Shulman G, Hardie D, and Young L. Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise. Am J Physiol Endocrinol Metab 285: E629-E636, 2003.
30. Crute B, Seefeld K, Gamble J, Kemp B, and Witters L. Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase. J Biol Chem 273: 35347-35354, 1998.
31. Daniel T and Carling D. Functional analysis of mutations in the gamma 2 subunit of AMP-activated protein kinase associated with cardiac hypertrophy and Wolff-Parkinson-White syndrome. J Biol Chem 277: 51017-51024, 2002.
32. 2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White Syndrome. Am J Physiol Heart Circ Physiol 290: H1942-H1951, 2006.
33. Davies S, Hawley S, Woods A, Carling D, Haystead T, and Hardie D. Purification of the AMP-activated protein kinase on ATP-gamma-sepharose and analysis of its subunit structure. Eur J Biochem 223: 351-357, 1994.
34. Davies S, Helps N, Cohen P, and Hardie D. 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377: 421-425, 1995.
35. Dennis S, Gevers W, and Opie L. Protons in ischemia: where do they come from; where do they go to? J Mol Cell Cardiol 23: 1077-1086, 1991.
36. Depre C, Rider M, and Hue L. Mechanisms of control of heart glycolysis. Eur J Biochem 258: 277-290, 1998.
37. Dyck J, Gao G, Widmer J, Stapleton D, Fernandez C, Kemp B, and Witters L. Regulation of 5′-AMP-activated protein kinase activity by the noncatalytic beta and gamma subunits. J Biol Chem 271: 17798-17803, 1996.
38. Dyck J, Kudo N, Barr A, Davies S, Hardie D, and Lopaschuk G. Phosphorylation control of cardiac acetyl-CoA carboxylase by cAMP-dependent protein kinase and 5′-AMP activated protein kinase. Eur J Biochem 262: 184-190, 1999.
39. Dyck J and Lopaschuk G. AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol 574: 95-112, 2006.
40. Ferrer A, Caelles C, Massot N, and Hegardt F. Activation of rat liver cytosolic 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase by adenosine 5′-monophosphate. Biochem Biophys Res Commun 132: 497-504, 1985.
41. Folmes C, Clanachan A, and Lopaschuk G. Fatty acids attenuate insulin regulation of 5′-AMP-activated protein kinase and insulin cardioprotection after ischemia. Circ Res 99: 3-5, 2006.
42. Fryer L, Parbu-Patel A, and Carling D. The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 277: 25226-25232, 2002.
43. Gao G, Fernandez C, Stapleton D, Auster A, Widmer J, Dyck J, Kemp B, and Witters L. Non-catalytic beta- and gamma-subunit isoforms of the 5′-AMP-activated protein kinase. J Biol Chem 271: 8675-8681, 1996.
44. Gollob M. Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome. Biochem Soc Trans 31: 228-231, 2003.
45. Gollob M, Green M, Tang A, Gollob T, Karibe A, Ali Hassan A, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski L, and Roberts R. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med 344: 1823-1831, 2001.
46. Hall J, Lopaschuk G, Barr A, Bringas J, Pizzurro R, and Stanley W. Increased cardiac fatty acid uptake with dobutamine infusion in swine is accompanied by a decrease in malonyl CoA levels. Cardiovasc Res 32: 879-885, 1996.
47. Hallows K. Emerging role of AMP-activated protein kinase in coupling membrane transport to cellular metabolism. Curr Opin Nephrol Hypertens 14: 464-467, 2005.
48. Halse RFL, McCormack JG, Carling D, and Yeaman SJ. Regulation of glycogen synthase by glucose and glycogen: a possible role for AMP-activated protein kinase. Diabetes 52: 9-15, 2003.
49. Hawley S, Boudeau J, Reid J, Mustard K, Udd L, Makela T, Alessi D, and Hardie D. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2: 28, 2003.
50. Hawley S, Davison M, Woods A, Davies S, Beri R, Carling D, and Hardie D. Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem 271: 27879-27887, 1996.
51. Hawley S, Pan D, Mustard K, Ross L, Bain J, Edelman A, Frenguelli B, and Hardie D. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2: 9-19, 2005.
52. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Hoglund P, Jarvinen H, Kristo P, Pelin K, Ridanpaa M, Salovaara R, Toro T, Bodmer W, Olschwang S, Olsen A, Stratton M, de la Chapelle A, and Aaltonen L. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391: 184-187, 1998.
53. Hendrickson S, St Louis J, Lowe J, and Abdel-aleem S. Free fatty acid metabolism during myocardial ischemia and reperfusion. Mol Cell Biochem 166: 85-94, 1997.
54. Hochachka P and Mommsen T. Protons and anaerobiosis. Science 219: 1391-1397, 1983.
55. Hong S, Leiper F, Woods A, Carling D, and Carlson M. Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci USA 100: 8839-8843, 2003.
56. Horman S, Beauloye C, Vertommen D, Vanoverschelde J, Hue L, and Rider M. Myocardial ischemia and increased heart work modulate the phosphorylation state of eukaryotic elongation factor-2. J Biol Chem 278: 41970-41976, 2003.
57. Horman S, Vertommen D, Heath R, Neumann D, Mouton V, Woods A, Schlattner U, Wallimann T, Carling D, Hue L, and Rider M. Insulin antagonizes ischemia-induced THR172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of SER485/491. J Biol Chem 281: 5335-5340, 2006.
58. Hudson E, Pan D, James J, Lucocq J, Hawley S, Green K, Baba O, Terashima T, and Hardie DG. A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias. Curr Biol 13: 861-866, 2003.
59. Hurley R, Anderson K, Franzone J, Kemp B, Means A, and LAW. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem 280: 29060-29066, 2005.
60. Inoki K, Zhu T, and Guan K. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115: 577-590, 2003.
61. Iseli T, Walter M, van Denderen B, Katsis F, Witters L, Kemp B, Michell B, and Stapleton D. AMP-activated protein kinase beta subunit tethers alpha and gamma subunits via its C-terminal sequence (186-270). J Biol Chem 280: 13395-13400, 2005.
62. Jefferson L, Wolpert E, Giger K, and Morgan H. Regulation of protein synthesis in heart muscle. 3 Effect of anoxia on protein synthesis. J Biol Chem 246: 2171-2178, 1971.
63. Jorgensen S, Viollet B, Andreelli F, Frosig C, Birk J, Schjerling P, Vaulont S, Richter E, and Wojtaszewski J. Knockout of the alpha2 but not alpha1 5′-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4- carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle. J Biol Chem 279: 1070-1079, 2004.
64. Kahn B, Alquier T, Carling D, and Hardie D. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1: 15-25, 2005.
65. Kammermeier H. Myocardial cell energetics. Adv Exp Med Biol 430: 89-96, 1997.
66. Kerbey A, Randle P, Cooper R, Whitehouse S, Pask H, and Denton R. Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. Biochem J 154: 327-348, 1976.
67. Kimball S, Siegfried B, and Jefferson L. Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J Biol Chem 279: 54103-54109, 2004.
68. Kira Y, Kochel P, Gordon E, and Morgan H. Aortic perfusion pressure as a determinant of cardiac protein synthesis. Am J Physiol Cell Physiol 246: C247-C258, 1984.
69. Kovacic S, Soltys C, Barr A, Shiojima I, Walsh K, and Dyck J. Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem 278: 39422-39427, 2003.
70. Krause U, Bertrand L, and Hue L. Control of p70 ribosomal protein S6 kinase and acetyl-CoA carboxylase by AMP-activated protein kinase and protein phosphatases in isolated hepatocytes. Eur J Biochem 269: 3751-3759, 2002.
71. Kuang M, Febbraio M, Wagg C, Lopaschuk G, and Dyck J. Fatty acid translocase/CD36 deficiency does not energetically or functionally compromise hearts before or after ischemia. Circulation 109: 1550-1557, 2004.
72. Kudo N, Barr A, Barr R, Desai S, and Lopaschuk G. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem 270: 17513-17520, 1995.
73. Kudo N, Gillespie J, Kung L, Witters L, Schulz R, Clanachan A, and Lopaschuk G. Characterization of 5′AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemia. Biochim Biophys Acta 1301: 67-75, 1996.
74. Kurien V and Oliver M. Free fatty acids during acute myocardial infarction. Prog Cardiovasc Dis 13: 361-373, 1971.
75. Lang T, Yu L, Tu Q, Jiang J, Chen Z, Xin Y, Liu G, and Zhao S. Molecular cloning, genomic organization, and mapping of PRKAG2, a heart abundant gamma2 subunit of 5′-AMP-activated protein kinase, to human chromosome 7q36. Genomics 70: 258-263, 2000.
76. Lehman J and Kelly D. Gene regulatory mechanisms governing energy metabolism during cardiac hypertrophic growth. Heart Fail Rev 7: 175-185, 2002.
77. Lei B, Matsuo K, Labinskyy V, Sharma N, Chandler M, Ahn A, Hintze T, Stanley W, and Recchia F. Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo. Proc Natl Acad Sci USA 102: 6966-6971, 2005.
78. Li J, Coven D, Miller E, Hu X, Young M, Carling D, Sinusas A, and Young L. Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart. Am J Physiol Heart Circ Physiol In press.
79. Li J, Hu X, Selvakumar P, Russell R, Cushman S, Holman G, and Young L. Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab 287: E834-E841, 2004.
80. Li J, Miller E, Ninomiya-Tsuji J, Russell R, and Young L. AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res 97: 872-879, 2005.
81. Light P, Wallace C, and Dyck J. Constitutively active adenosine monophosphate-activated protein kinase regulates voltage-gated sodium channels in ventricular myocytes. Circulation 107: 1962-1965, 2003.
82. Longnus S, Wambolt R, Barr R, Lopaschuk G, and Allard M. Regulation of myocardial fatty acid oxidation by substrate supply. Am J Physiol Heart Circ Physiol 281: H1561-H1567, 2001.
83. Longnus S, Wambolt R, Parsons H, Brownsey R, and Allard M. 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms. Am J Physiol Regul Integr Comp Physiol 284: R936-R944, 2003.
84. Lopaschuk G, Belke D, Gamble J, Itoi T, and Schonekess B. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochem Biophys Acta 1213: 263-276, 1994.
85. Lopaschuk G, Collins-Nakai R, Olley P, Montague T, McNeil G, Gayle M, Penkoske P, and Finegan B. Plasma fatty acid levels in infants and adults after myocardial ischemia. Am Heart J 128: 61-67, 1994.
86. Lopaschuk G and Spafford M. Energy substrate utilization by isolated working hearts from newborn rabbits. Am J Physiol Heart Circ Physiol 258: H1274-H1280, 1990.
87. Lopaschuk G, Spafford M, Davies N, and Wall S. Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ Res 66: 546-553, 1990.
88. Lopaschuk G and Stanley W. Glucose metabolism in the ischemic heart. Circulation 95: 313-315, 1997.
89. Luiken J, Coort S, Willems J, Coumans W, Bonen A, van der Vusse G, and Glatz J. Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. Diabetes 52: 1627-1634, 2003.
90. MacRae C, Ghaisas N, Kass S, Donnelly S, Basson C, Watkins H, Anan R, Thierfelder L, McGarry K, Rowland E, McKenna W, Seidman J, and Seidman C. Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 96: 1216-1220, 1995.
91. Makinde AO, Gamble J, and Lopaschuk GD. Upregulation of 5′-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit. Circ Res 80: 482-489, 1997.
92. Marsin A, Bertrand L, Rider M, Deprez J, Beauloye C, Vincent M, Van den Berghe G, Carling D, and Hue L. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr Biol 10: 1247-1255, 2000.
93. Merrill G, Kurth E, Hardie D, and Winder W. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol Endocrinol Metab 273: E1107-E1112, 1997.
94. Minokoshi Y, Kim Y, Peroni O, Fryer L, Muller C, Carling D, and Kahn B. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415: 339-343, 2002.
95. Mitchelhill K, Stapleton D, Gao G, House C, Michell B, Katsis F, Witters L, and Kemp B. Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. J Biol Chem 269: 2361-2364, 1994.
96. Mu J, Brozinick J, Valladares O, Bucan M, and Birnbaum M. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell 7: 1085-1094, 2001.
97. Mueller H and Ayres S. Metabolic response of the heart in acute myocardial infarction in man. Am J Cardiol 42: 363-371, 1978.
98. Muoio D, Seefeld K, Witters L, and Coleman R. AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochem J 338: 783-791, 1999.
99. Musi N, Hirshman M, Arad M, Xing Y, Fujii N, Pomerleau J, Ahmad F, Berul C, Seidman J, Tian R, and Goodyear L. Functional role of AMP-activated protein kinase in the heart during exercise. FEBS Lett 579: 2045-2050, 2005.
100. Nagoshi T, Matsui T, Aoyama T, Leri A, Anversa P, Li L, Ogawa W, del Monte F, Gwathmey J, Grazette L, Hemmings B, Kass D, Champion H, and Rosenzweig A. PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest 115: 2128-2138, 2005.
101. Nascimben L, Ingwall J, Lorell B, Pinz I, Schultz V, Tornheim K, and Tian R. Mechanisms for increased glycolysis in the hypertrophied rat heart. Hypertension 44: 662-667, 2004.
102. Newsholme E and Randle P. Regulation of glucose upake by muscle. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan diabetes, starvation, hypophysectomy, and adrenalectomy, on the concentrations of hexose phosphates, nucleotides, and inorganic phosphate in perfused rat heart. Biochem J 93: 641-651, 1964.
103. Oliver M and Opie L. Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias. Lancet 343: 155-158, 1994.
104. Pelletier A, Joly E, Prentki M, and Coderre L. Adenosine 5′-monophosphate-activated protein kinase and p38 mitogen-activated protein kinase participate in the stimulation of glucose uptake by dinitrophenol in adult cardiomyocytes. Endocrinology 146: 2285-2294, 2005.
105. Ponticos M, Lu Q, Morgan J, Hardie D, Partridge T, and Carling D. Dual regulation of the AMP-activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle. EMBO J 17: 1688-1699, 1998.
106. Russell R, Bergeron R, Shulman G, and Young L. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am J Physiol Heart Circ Physiol 277: H643-H649, 1999.
107. Russell R, Li J, Coven D, Pypaert M, Zechner C, Palmeri M, Giordano F, Mu J, Birnbaum M, and Young L. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest 114: 495-503, 2004.
108. Saddik M, Gamble J, Witters L, and Lopaschuk G. Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. J Biol Chem 268: 25836-25845, 1993.
109. Saddik M and Lopaschuk G. Myocardial triglyceride turnover and contribution to energy substrate utilization in isolated working rat hearts. J Biol Chem 266: 8162-8170, 1991.
110. Sakamoto K, Zarrinpashneh E, Budas G, Pouleur A, Dutta A, Prescott A, Vanoverschelde J, Ashworth A, Jovanovic A, Alessi D, and Bertrand L. Deficiency of LKB1 in heart prevents ischemia-mediated activation of AMPKα2 but not AMPKα1. Am J Physiol Endocrinol Metab 290: E780-E788, 2006.
111. Sakoda H, Fujishiro M, Fujio J, Shojima N, Ogihara T, Kushiyama A, Fukushima Y, Anai M, Ono H, Kikuchi M, Horike N, Viana A, Uchijima Y, Kurihara H, and Asano T. Glycogen debranching enzyme association with beta-subunit regulates AMP-activated protein kinase activity. Am J Physiol Endocrinol Metab 289: E474-E481, 2005.
112. Schulz E, Anter E, Zou M, and Keaney JJ. Estradiol-mediated endothelial nitric oxide synthase association with heat shock protein 90 requires adenosine monophosphate-dependent protein kinase. Circulation 111: 3473-3480, 2005.
113. Scott J, Hawley S, Green K, Anis M, Stewart G, Scullion G, Norman D, and Hardie D. CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J Clin Invest 113: 274-284, 2004.
114. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel D, Kumada M, Sato K, Schiekofer S, Ohashi K, Funahashi T, Colucci W, and Walsh K. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 10: 1384-1389, 2004.
115. Shibata R, Sato K, Pimentel D, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, and Walsh K. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med 11: 1096-1103, 2005.
116. Shiojima I, Sato K, Izumiya Y, Schiekofer S, Ito M, Liao R, Colucci W, and Walsh K. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 115: 2108-2118, 2005.
117. Sidhu J, Rajawat Y, Rami T, Gollob M, Wang Z, Yuan R, Marian A, DeMayo F, Weilbacher D, Taffet G, Davies J, Carling D, Khoury D, and Roberts R. Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome. Circulation 111: 21-29, 2005.
118. Soltys C, Kovacic S, and Dyck J. Activation of Cardiac AMP-activated protein kinase (AMPK) by LKB1 expression or chemical hypoxia is blunted by increased Akt activity. Am J Physiol Heart Circ Physiol 290: H2472-H2479, 2006.
119. Stapleton D, Mitchelhill K, Gao G, Widmer J, Michell B, Teh T, House C, Fernandez C, Cox T, Witters L, and Kemp B. Mammalian AMP-activated protein kinase subfamily. J Biol Chem 271: 611-614, 1996.
120. Sugden P and Clerk A. Cellular mechanisms of cardiac hypertrophy. J Mol Med 76: 725-746, 1998.
121. Sutherland C, Hawley S, McCartney R, Leech A, Stark M, Schmidt M, and Hardie D. Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr Biol 13: 1299-1305, 2003.
122. Taegtmeyer H, Golfman L, Sharma S, Razeghi P, and van Arsdall M. Linking gene expression to function: metabolic flexibility in the normal and diseased heart. Ann NY Acad Sci 1015: 202-213, 2004.
123. Taegtmeyer H, Hems R, and Krebs H. Utilization of energy-providing substrates in the isolated working rat heart. Biochem J 186: 701-711, 1980.
124. Terada S, Goto M, Kato M, Kawanaka K, Shimokawa T, and Tabata I. Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochem Biophys Res Commun 296: 350-354, 2002.
125. Thornton C, Snowden M, and Carling D. Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle. J Biol Chem 273: 12443-12450, 1998.
126. Tian R, Musi N, D'Agostino J, Hirshman M, and Goodyear L. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation 104: 1664-1669, 2001.
127. Tong H, Chen W, London R, Murphy E, and Steenbergen C. Preconditioning enhanced glucose uptake is mediated by p38 MAP kinase not by phosphatidylinositol 3-kinase. J Biol Chem 275: 11981-11986, 2000.
128. Vavvas D, Apazidis A, Saha A, Gamble J, Patel A, Kemp B, Witters L, and Ruderman N. Contraction-induced changes in acetyl-CoA carboxylase and 5′-AMP-activated kinase in skeletal muscle. J Biol Chem 272: 13255-13261, 1997.
129. Verhoeven A, Woods A, Brennan C, Hawley S, Hardie D, Scott J, Beri R, and Carling D. The AMP-activated protein kinase gene is highly expressed in rat skeletal muscle. Alternative splicing and tissue distribution of the mRNA. Eur J Biochem 228: 236-243, 1995.
130. Villena J, Viollet B, Andreelli F, Kahn A, Vaulont S, and Sul H. Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit. Diabetes 53: 2242-2249, 2004.
131. Viollet B, Andreelli F, Jorgensen S, Perrin C, Geloen A, Flamez D, Mu J, Lenzner C, Baud O, Bennoun M, Gomas E, Nicolas G, Wojtaszewski J, Kahn A, Carling D, Schuit F, Birnbaum M, Richter E, Burcelin R, and Vaulont S. The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest 111: 91-98, 2003.
132. Wambolt R, Henning S, English D, Dyachkova Y, Lopaschuk G, and Allard M. Glucose utilization and glycogen turnover are accelerated in hypertrophied rat hearts during severe low-flow ischemia. J Mol Cell Cardiol 31: 493-502, 1999.
133. Watt M, Steinberg G, Chen Z, Kemp B, and Febbraio M. Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes. J Physiol 574: 139-147, 2006.
134. Winder W and Hardie D. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol Endocrinol Metab 270: E299-E304, 1996.
135. Witters L and Kemp B. Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5′-AMP-activated protein kinase. J Biol Chem 267: 2864-2867, 1992.
136. Wojtaszewski J, Jorgensen S, Hellsten Y, Hardie D, and Richter E. Glycogen-dependent effects of 5-aminoimidazole-4-carboxamide (AICA)-riboside on AMP-activated protein kinase and glycogen synthase activities in rat skeletal muscle. Diabetes 51: 284-292, 2002.
137. Woods A, Dickerson K, Heath R, Hong S, Momcilovic M, Johnstone S, Carlson M, and Carling D. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2: 21-33, 2005.
138. Woods A, Vertommen D, Neumann D, Turk R, Bayliss J, Schlattner U, Wallimann T, Carling D, and Rider M. Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis. J Biol Chem 278: 28434-28442, 2003.
139. Xing Y, Musi N, Fujii N, Zou L, Luptak I, Hirshman M, Goodyear L, and Tian R. Glucose metabolism and energy homeostasis in mouse hearts overexpressing dominant negative alpha2 subunit of AMP-activated protein kinase. J Biol Chem 278: 28372-28377, 2003.
140. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn B, and Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8: 1288-1295, 2002.
141. Yang J and Holman G. Insulin and contraction stimulate exocytosis, but increased AMP-activated protein kinase activity resulting from oxidative metabolism stress slows endocytosis of GLUT4 in cardiomyocytes. J Biol Chem 280: 4070-4078, 2005.
142. Yang J and Holman G. Long-term metformin treatment stimulates cardiomyocyte glucose transport through an AMPK-dependent reduction in GLUT4 endocytosis. Endocrinology 147: 2728-2736, 2006.
143. Yeh L, Lee K, and Kim K. Regulation of rat liver acetyl-CoA carboxylase. Regulation of phosphorylation and inactivation of acetyl-CoA carboxylase by the adenylate energy charge. J Biol Chem 255: 2308-2314, 1980.
144. Yu H, Fujii N, Hirshman M, Pomerleau J, and Goodyear L. Cloning and
145. Zong H, Ren J, Young L, Pypaert M, Mu J, Birnbaum M, and Shulman G. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99: 15983-15987, 2002.
146. Zou L, Shen M, Arad M, He H, Lofgren B, Ingwall J, Seidman C, Seidman J, and Tian R. N488I mutation of the gamma2-subunit results in bidirectional changes in AMP-activated protein kinase activity. Circ Res 97: 323-328, 2005.