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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2007, Número 6

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Rev Invest Clin 2007; 59 (6)


La AMPK como un sensor de energía celular y su función en el organismo

Miranda N, Tovar AR, Palacios B, Torres N

Idioma: Español
Referencias bibliográficas: 98
Paginas: 458-469
Archivo PDF: 194.53 Kb.


RESUMEN

La cinasa activada por monofosfato de adenina (AMP), conocida por sus siglas en inglés como AMPK, es un complejo heterotrimérico que se activa con el incremento en la relación AMP/ATP, por lo que se considera un sensor de energía celular que contribuye a regular el balance energético y la ingesta calórica. La AMPK es activada por la cinasa LKB1 y puede fosforilar una serie de enzimas involucradas en el anabolismo para prevenir el consumo de ATP y en el catabolismo para incrementar la generación de ATP. Asimismo, disminuye o incrementa la expresión de algunos genes involucrados tanto en la lipogénesis y en la biogénesis mitocondrial, entre otros. La AMPK está presente en la mayoría de los órganos incluyendo el hígado, músculo esquelético, corazón, hipotálamo e incluso en las células adiposas. Además, la AMPK es activada en el cerebro para estimular el apetito debido a la depleción de energía. Ya que la AMPK participa en la regulación de la glucólisis, en la entrada de glucosa, en la oxidación de lípidos, en la síntesis de ácidos grasos, en la síntesis de colesterol y en la gluconeogénesis ha sido considerada como una enzima blanco en el posible tratamiento de algunas enfermedades como lo son la obesidad, la diabetes mellitus tipo 2 y la esteatosis hepática. En esta revisión se da un panorama general de la estructura de la AMPK, de sus activadores y de la función que lleva a cabo en los diversos tejidos.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Kahn BB, Alquier T, Carling D, Hardie G. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005; 1: 15-25.

  2. Carling D. The AMP-activated protein kinase cascade—a unifying system for energy control. Trends Biochem Sci 2004; 29: 18-24.

  3. Steinberg GR, Macaulay SL, Febbraio MA, Kemp BE. AMP-activated protein kinase—the fat controller of the energy railroad. Can J Physiol Pharmacol 2006; 84: 655-65.

  4. Hardie DG, Salt IP, Hawley SA, Davies SP. AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J 1999; 338: 717-22.

  5. Alessi DR, Sakamoto K, Bayascas JR. LKB1-dependent signaling pathways. Annu Rev Biochem 2006; 75: 137-63.

  6. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, et al. A serine/threonine kinase gene defective in Peutz- Jeghers syndrome. Nature 1998; 391: 184-87.

  7. Carling D, Fryer LG, Woods A, Daniel T, Jarvie SL, Whitrow H. Bypassing the glucose/fatty acid cycle: AMP-activated protein kinase. Biochem Soc Trans 2003; 31: 1157-60.

  8. Birnbaum MJ. Activating AMP-activated protein kinase without AMP. Mol Cell 2005; 19: 289-90.

  9. Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, et al. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2005; 2: 9-19.

  10. Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res 2007; 100: 328-41.

  11. Evans AM. AMP-activated protein kinase and the regulation of Ca2+ signalling in O2-sensing cells. J Physiol 2006; 574: 113-23.

  12. Hardie DG, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 1998; 67: 821-55.

  13. Hardie DG, Hawley SA. AMP-activated protein kinase: the energy charge hypothesis revisited. BioEssays 2001; 23: 1112-19.

  14. Hardie DG. New roles for the LKB1—>AMPK pathway. Curr Opin Cell Biol 2005; 17: 167-73.

  15. Corton JM, Gillespie JG, Hardie DG. Role of the AMP-activated protein kinase in the cellular stress response. Curr Biol 1994; 4: 315-24.

  16. Cheung PCF, Salt IP, Davies SP, Hardie DG, Carling D. Characterization of AMP-activated protein kinase g subunit isoforms and their role in AMP binding. Biochem J 2000; 346: 659-69.

  17. Kemp BE. Bateman domains and adenosine derivatives form a binding contract. J Clin Invest 2004; 113: 182-4.

  18. Adams J, Chen ZP, Van Denderen BJ, Morton CJ, Parker MW, Witters LA, et al. Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site. Protein Sci 2004; 13: 155-65.

  19. Hawley SA, Davison M, Woods A, Davies SP, K. BR, Carling D, Hardie DG. 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 1996; 271: 27879-87.

  20. Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LGD, Neumann D, et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003; 13: 2004-08.

  21. Hardie DG. The AMP-activated protein kinase pathway-new players upstream and downstream. J Cell Sci 2004; 117: 5479- 87.

  22. Winder WW, Hardie DG. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol 1996; 270: E299-E304.

  23. Merrill GF, Kurth EJ, Hardie DG, Winder WW. AICA riboside oncreases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 1997; 273: E1107-E1112.

  24. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody JW, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001; 108: 1167-74.

  25. Fryer LGD, Parbu-Patel A, Carling D. The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 2002; 277: 25226-32.

  26. Ye JM, Dzamko N, Hoy AJ, Iglesias MA, Kemp BE, Kraegen E. Rosiglitazone treatment enhances acute AMP-activated protein kinase mediated muscle and adipose tissue glucose uptake in high fat fed rats. Diabetes 2006; 55: 2797-804.

  27. Lessard SJ, Chen ZP, Watt MJ, Hashem M, Reid JJ, Febbraio MA, et al. Chronic rosiglitazone treatment restores AMPKalpha2 activity in insulin-resistant rat skeletal muscle. Am J Physiol Endocrinol Metab 2006; 290: E251-E257.

  28. Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW. 5’ AMP-activated protein kinase activation causes GLUT 4 translocation in skeletal muscle. Diabetes 1999; 48: 1667-71.

  29. Suwa M, Egashira T, Nakano H, Sasaki H, Kumagai S. Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. J Appl Physiol 2006; 101: 1685-92.

  30. McCarty MF. AMPK activation as a strategy for reversing the endothelial lipotoxicity underlying the increased vascular risk associated with insulin resistance syndrome. Med Hypotheses 2005; 64: 1211-5.

  31. Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-aminoimidazole- 4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cell? Eur J Biochem 1995; 229: 558-65.

  32. Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, et al. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol 2006; 574: 41-53.

  33. Assifi MM, Suchankova G, Constant S, Prentki M, Saha K, Ruderman NB. AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved-carbohydrate-refed rats. Am J Physiol Endocrinol Metab 2005; 289: E794-E800.

  34. Muoio DM, Seefeld K, Witters LA, Coleman RA. 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 1999; 338(Pt 3): 783-91.

  35. Horman S, Browne GJ, Krause U, Patel JV, Vertommen D, Bertrand L, et al. Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 2002; 12: 1419-23.

  36. Leclerc I, Kahn A, Doiron B. The 5’-AMP-activated protein kinase inhibits the transcriptional stimulation by glucose in liver cells, acting through the glucose response complex. FEBS Lett 1998; 431: 180-4.

  37. Tomita K, Tomiya G, Ando S, Kitamura N, Koizumi H, Kato S, et al. AICAR, an AMPK activator, has protective effects on alcohol- induce fatty liver in rats. Alcohol Clin Exp Res 2005; 29: 240S-245S.

  38. Kawaguchi T, Osatomi K, Yamashita H, Kabashima T, Uyeda K. Mechanism for fatty acid “sparing” effect on glucose-induce transcription. Regulation of carbohydrate responsive elementbinding protein by AMP-activated protein kinase. J Biol Chem 2002; 277: 3829-35.

  39. Kawaguchi T, Takenoshita M, Kabshima T, Uyeda K. Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/ dephosphorylation of the carbohydrate response element binding protein. Proc Natl Acad Sci USA 2001; 98: 13710-15.

  40. Leclerc I, Lenzner C, Gourdon L, Vaulonts S, Khan A, Viollet B. Hepatocyte nuclear factor-4 a involved in type 1 maturityonset diabetes of the young is anovel target of AMP-activated protein kinase. Diabetes 2001; 59: 1515-21.

  41. Torres N, Torre-Villalvazo I, Tovar AR. Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders. J Nutr Biochem 2006; 17: 365-73.

  42. Carrasco-Chaumel E, Rosello-Catafau J, Bartrons R, Franco-Gou R, Xaus C, Casillas A, et al. Adenosine monophosphate-activated protein kinase and nitric oxide in rat steatotic liver transplantation. J Hepatol 2005; 43: 997-1006.

  43. Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, et al. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 2005; 54: 1331-9.

  44. Watt MJ, Dzamko N, Thomas WG, Rose-John S, Ernst M, Carling D, et al. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 2006; 12: 541-8.

  45. Sahlin K, Tonkonogi M, Soderlund K. Energy supply and muscle fatigue in humans. Acta Physiol Scand 1998; 162: 261-6.

  46. Winder WW, Hardie DG. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol 1996; 270: E299-E304.

  47. Hayashi T, Hirshman MF, Kurth EJ, Winder WW, Goodyear LJ. Evidence for 5’ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 1998; 47: 1369-73.

  48. Saha AK, Schwarsin AJ, Roduit R, Masse F, Kaushik V, Tornheim K, et al. Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-beta -Dribofuranoside. J Biol Chem 2000; 275: 24279-83.

  49. Watt MJ, Steinberg GR, Chen ZP, Kemp BE, Febbraio MA. Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes. J Physiol 2006; 574: 139-47.

  50. Ellingson WJ, Chesser DG, Winder WW. Effects of 3-phosphoglycerate and other metabolites on the activation of AMP-activated protein kinase by LKB1-STRAD-MO25. Am J Physiol Endocrinol Metab 2007; 292: E400-E407.

  51. Hardie DG, Scott JW, Pan DA, Hudson ER. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett 2003; 546: 113-20.

  52. Abu-Elheiga L, Matzuk MM, Abo-Hashema KA, Wakil SJ. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 2001; 291: 2613-6.

  53. Park H, Kaushik VK, Constant S, Prentki M, Przybytkowski E, Ruderman NB, Saha AK. Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J Biol Chem 2002; 277: 32571-7.

  54. Saha AK, Ruderman NB. Malonyl-CoA and AMP-activated protein kinase: an expanding partnership. Mol Cell Biochem 2003; 253: 65-70.

  55. Wojtaszewski JF, Nielsen P, Hansen BF, Richter EA, Kiens B. Isoform-specific and exercise intensity-dependent activation of 5’-AMP-activated protein kinase in human skeletal muscle. J physiol 2000; 528: 221-6.

  56. Chen ZP, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, et al. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes 2003; 52: 2205-12.

  57. Derave W, Ai H, Ihlemann J, Witters LA, Kristiansen S, Richter EA, Ploug T. Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle. Diabetes 2000; 49: 1281-7.

  58. Hardie DG. Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 2003; 144: 5179-83.

  59. Thong FS, Bilan PJ, Klip A. The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic. Diabetes 2007; 56: 414-23.

  60. Fryer LG, Foufelle F, Barnes K, Baldwin SA, Woods A, Carling D. Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells. Biochem J 2002; 363: 167-74.

  61. Winder WW. Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle. J Appl Physiol 2001; 91: 1017-28.

  62. Reznick RM, Shulman GI. The role of AMP-activated protein kinase in mitochondrial biogenesis. J Physiol 2006; 574: 33-9.

  63. Sriwijitkamol A, Ivy JL, Christ-Roberts C, DeFronzo RA, Mandarino LJ and Musi N. LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training. Am J Physiol Endocrinol Metab 2006; 290: E925-E932.

  64. Musi N, Goodyear LJ. Targeting the AMP-activated protein kinase for the treatment of type 2 diabetes. Curr Drug Targets Immune Endocr Metabol Disord 2002; 2: 119-27.

  65. Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 2002; 51: 2074-81.

  66. Horikoshi M, Hara K, Ohashi J, Miyake K, Tokunaga K, Ito C, et al. A polymorphism in the AMPKalpha2 subunit gene is associated with insulin resistance and type 2 diabetes in the Japanese population. Diabetes 2006; 55: 919-23.

  67. Steinberg GR. Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance. Cell Cycle 2007; 6: 888-94.

  68. Cheng SW, Fryer LG, Carling D, Shepherd PR. Thr 2446 is a novel mammalian target of rapamycin (mTor) phosphorylation site regulated by nutrient status. J Biol Chem 2004; 279: 15719-22.

  69. Ju JS, Gitcho MA, Casmaer CA, Patil PB, Han DG, Spencer SA, Fisher JS. Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase. Am J Physiol Cell Physiol 2007; 292: C564-C572.

  70. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, et al. A central role for JNK in obesity and insulin resistance. Nature 2002; 420: 333-6.

  71. Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, et al. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun 2005; 332: 885-91.

  72. Sullivan JE, Brocklehurst KJ, Marley AE, Carey F, Carling D, Beri RK. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett 1994; 353: 33-6.

  73. Garton AJ, Campbell DG, Carling D, Hardie DG, Colbran RJ, Yeaman SJ. Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein kinase. A possible antilipolytic mechanism. Eur J Biochem 1989; 179: 249-54.

  74. Yin W, Mu J, Birnbaum MJ. Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis In 3T3-L1 adipocytes. J Biol Chem 2003; 278: 43074-80.

  75. Sponarova J, Mustard KJ, Horakova O, Flachs P, Rossmeisl M, Brauner P, et al. Involvement of AMP-activated protein kinase in fat depot-specific metabolic changes during starvation. FEBS Lett 2005; 579: 6105-10.

  76. Daval M, Foufelle F, Ferre P. Functions of AMP-activated protein kinase in adipose tissue. J Physiol 2006; 574: 55-62.

  77. Moule SK, Denton RM. The activation of p38 MAPK by the beta-adrenergic agonist isoproterenol in rat epididymal fat cells. FEBS Lett 1998; 439: 287-90.

  78. Ahima RS. Adipose tissue as an endocrine organ. Obesity (Silver Spring) 2006; 14(Suppl. 5): 242S-249S.

  79. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002; 415: 339-43.

  80. Kola B, Boscaro M, Rutter GA, Grossman AB, Korbonits M. Expanding role of AMPK in endocrinology. Trends Endocrinol Metab 2006; 17: 205-15.

  81. Orci L, Cook WS, Ravazzola M, Wang MY, Park BH, Montesano R, Unger RH. Rapid transformation of white adipocytes into fat-oxidizing machines. Proc Natl Acad Sci USA 2004; 101: 2058-63.

  82. Ruderman NB, Keller C, Richard AM, Saha AK, Luo Z, Xiang X, et al. Interleukin-6 Regulation of AMP-Activated Protein Kinase: Potential Role in the Systemic Response to Exercise and Prevention of the Metabolic Syndrome. Diabetes 2006; 55(Suppl. 2): S48-S54.

  83. Dyck JR, Lopaschuk GD. AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol 2006; 574: 95-112.

  84. Browne GJ, Finn SG, Proud CG. 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 2004; 279: 12220-31.

  85. Li J, Hu X, Selvakumar P, Russell RR 3rd, Cushman SW, Holman GD, Young LH. Role of the nitric oxide pathway in AMPKmediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab 2004; 287: E834-E841.

  86. Bertrand L, Ginion A, Beauloye C, Hebert AD, Guigas B, Hue L, Vanoverschelde JL. 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 2006; 291: H239-H250.

  87. Zhang L, He H, Balschi JA. Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytoslic AMP concentration. Am J Physiol Heart Circ Physiol 2007; In Press DOI:10.1152.

  88. Daniel T, 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 2002; 277: 51017-24.

  89. Arad M, Seidman CE, Seidman JG. AMP-activated protein kinase in the heart: role during health and disease. Circ Res 2007; 100: 474-88.

  90. Luptak I, Shen M, He H, Hirshman MF, Musi N, Goodyear LJ, et al. Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage. J Clin Invest 2007; 117: 1432-39.

  91. Hudson ER, Pan DA, James J, Lucocq JM, Hawley SA, Green KA, et al. A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias. Curr Biol 2003; 13: 861-6.

  92. Cai F, Gyulkhandanyan AV, Wheeler MB, Belsham DD. Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin. J Endocrinol 2007; 192: 605-14.

  93. Turnley AM, Stapleton D, Mann RJ, Witters LA, Kemp BE, Bartlett PF. Cellular distribution and developmental expression of AMP-activated protein kinase isoforms in mouse central nervous system. J Neurochem 1999; 72: 1707-16.

  94. Xue B, Kahn BB. AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol 2006; 574: 73-83.

  95. Simler N, Malgoyre A, Koulmann N, Alonso A, Peinnequin A, Bigard X. Hypoxic stimulus alters hypothalamic AMP-activated protein kinase phosphorylation concomitant to hypophagia. J Appl Physiol 2007.

  96. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 2004; 428: 569-74.

  97. Ramamurthy S, Ronnett GV. Developing a head for energy sensing: AMP-activated protein kinase as a multifunctional metabolic sensor in the brain. J Physiol 2006; 574: 85-93.

  98. Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, et al. AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 2004; 279: 12005-8.




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