Chinese Bulletin of Life Sciences AMP. (AMP-activated protein kinase, AMPK) Advances in the studies of AMP-activated protein kinase

Transcription

1 Chinese Bulletin of Life Sciences Vol. 17, No. 2 Apr., (2005) AMP (AMP-activated protein kinase, ) AMP Q555.7 A Advances in the studies of AMP-activated protein kinase FU Qing-Ying, GAO Yu-Qi* (Key Laboratory of High Altitude Physiology and Mountain Sickness of PLA, Department of Pathophysiology and High Altitude Physiology, Third Military Medical University, Chongqing , China) Abstract: The AMP-activated protein kinase is found in all eukaryotic cells. Once activated, the kinase switches on -producing catabolic pathways and switches off -consuming processes,both via direct phosphorylation of downstream targets, and thus is called a cellular energy regulator. A variety of novel downstream target proteins have been discovered recently, which provide new insight into elucidating precise functions of AMP-activated protein kinase. Key words: AMP-activated protein kinase; energy metabolism; adenosine monophosphate 1 α (63kD) β (30kD) γ (37~63kD) α β γ α1 α2 β1 β2 γ1 γ2 γ3 α N C N C β γ C AMP N C α β γ β γ α α β γ α Thr172 β N KIS ASC ASC α β γ (1977 ) (1962 ) *

2 148 [1] KIS KIS N- β [2] γ N γ1 γ2 γ3 N γ CBS AMP β γ β N γ N 2 α1 α 2 α2 [3] α2 α1 [4] α1 α2 -α2 [5] β1 leptin α2 leptin - leptin [7] adiponectin adiponectin [8~10] 2 ( ) [11] ONOO -[12] [13] AMP AMP/ 3.3 (AMP-activated protein kinase kinase K) K α Thr172 [14] AMP/ β 2 γ 1 γ 2 γ 3 [6] Thr172 STRADα/β MO25α/β [16] [17] [15] A AMP/ (5- amino-4-imidazolecarboxamide-riboside, AICAR) AICAR ZMP(5-aminoimidazole-4-carboxamide-1-β-Dribofuranosyl-5-monophate) ZMP AMP AICAR ZMP AMP ( -1, 6- ) 3.2 AMP (leptin) (adiponectin) leptin [18] C75 Compound C [11] α AICAR 4 [19] [20] AICAR

3 [22] [21] [28] X ) p300 ( E1a p53 GATA4) -2-2, [23] ( 1, 6- ) 4.2 CoA CoA CoA 4.3 (mammalian target of rapamycin, mtor) mrna mtor mtor 4E 70kD S6 S6 4G mtor [25] mtor [26] mtor Horman AICAR 2(eukaryotic elongation factor-2, eef-2) eef-2 [27] eef p300 Ser89 p300 ( [24] 1(hypoxia-inducible factor-1, HIF-1) HIF-1 HIF-1 HIF-1 HIF-1 HIF-1 HIF-1 HIF-1 3 /Akt [29] [30] 4α(hepatocyte nuclear factor-4α, ) DNA -2 [31] γ 1α [32] 1C (sterol-regulatory-element-binding protein-1c, SREBP1c) (fatty acid synthase, FAS) SREBP1c FAS mrna [34] [33] L L 4.5 AICAR c-myc c-jun N caspase β [35~36] caspase [37] AICAR κb(nuclear factor-kappab, NF-κB)

4 150 [38] NF-κB AICAR 4.6 Akt [39] [40] [7] [48] β- p16ink4a RNA HuR HuR HuR HuR [49] [41] 4.7 camp [42] 5 AICAR ( EBP)- α2 4.8 α 1β 6) NF-κB IκB α/β CCAAT/ (CCAAT/enhancer-binding protein, C/ C/EBP α2 [43~44] (cystic fibrosis transmembrane conductance regulator, CFTR) Cl - camp CFTR CFTR (1) AICAR AICAR AICAR (2) K camp CFTR Cl - camp Cl - [45] CFTR Na + [46] 4.9 [47] leptin agouti- [1] Hudson E R, Pan D A, James J,. A novel domain in AMPactivated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias., 2003, 13(10): 861~866 [2] Polekhina G, Gupta A, Michell B J,. β subunit targets metabolic stress sensing to glycogen., 2003, 13(10): 867~871 [3] Turnley A M, Stapleton D, Mann R J,. Cellular distribution and developmental expression of AMP-activated protein kinase isoforms in mouse central nervous system., 1999, 72(4): 1707~1716 [4] Culmsee C, Monning J, Kemp B E,. AMP-activated protein kinase is highly expressed in neurons in the develop-

5 ing rat brain and promotes neuronal survival following glucose deprivation., 2001, 17(1): 45~58 [5] Dyck J R, Kudo N, Barr A J,. Phosphorylation control of cardiac acetyl-coa carboxylase by camp-dependent protein kinase and 5'-AMP activated protein kinase., 1999, 262(1): 184~190 [6] Salt I, Celler J W, Hawley S A,. AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing the α2 isoform., 1998, 334(Pt 1): 177~187 [7] Minokoshi Y, Alquier T, Furukawa N,. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus., 2004, 428(6982): 569~574 [8] Shibata R, Ouchi N, Kihara S,. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of AMP-activated protein kinase signaling., 2004, 279(27): 28670~28674 [9] Ouchi N, Kobayashi H, Kihara S,. Adiponectin stimulates angiogenesis by promoting cross-talk between AMPactivated protein kinase and Akt signaling in endothelial cells., 2004, 279(2): 1304~1309 [10] Kobayashi H, Ouchi N, Kihara S,. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin., 2004, 94(4): e27~e31 [11] Zhou G C, Myers R, Li Y,. Role of AMP-activated protein kinase in mechanism of metformin action., 2001,108(8): 1167~1174 [12] Zou M H, Hou X Y, Shi C M,. Activation of 5'-AMPactivated kinase is mediated through c-src and phosphoinositide 3-kinase activity during hypoxia-reoxygenation of bovine aortic endothelial cells., 2003, 278(36): 34003~34010 [13] Daniel T, Carling D. Expression and regulation of the AMPactivated protein kinase-snf1 (sucrose non-fermenting 1) kinase complexes in yeast and mammalian cells: studies using chimaeric catalytic subunits., 2002, 365(Pt 3): 629~638 [14] Hong S P, Leiper F C, Woods A,. Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases., 2003, 100(15): 8839~8843 [15] Shaw R J, Kosmatka M, Bardeesy N,. The tumor suppressor kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress., 2004, 101(10): 3329~3335 [16] Hawley S A, Boudeau J, Reid J L,. Complexes between the tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade., 2003, 2(4): 28 [17] Lizcano J M, Goransson O, Toth R,. is a master kinase that activates 13 kinases of the subfamily, including MARK/PAR-1., 2004, 23(4): 833~843 [18] Landree L E, Hanlon A L, Strong D W,. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism., 2004, 279(5): 3817~3827 [19] Lemieux K, Konrad D, Klip A,. The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38 mitogen-activated protein kinases α and β in skeletal muscle., 2003, 17(12): 1658~1665 [20] Sakoda H, Ogihara T, Anai M,. Activation of is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes., 2002, 282(6): E1239~E1244 [21] Mu J, Brozinick J T, Valladares O,. A role for AMPactivated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle., 2001, 7 (5): 1085~1094 [22] Nielsen J N, Jorgensen S B, Frosig C,. A possible role for AMP-activated protein kinase in exercise-induced glucose utilization: insights from humans and transgenic animals., 2003, 31(Pt 1): 186~190 [23] Marsin A S, Bouzin C, Bertrand L,. The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6- phosphofructo-2-kinase., 2002, 277(34): 30778~30783 [24] Arsham A M, Howell J J, Simon M C,. A novel hypoxiainducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets., 2003, 278(32): 29655~29660 [25] Kimura N, Tokunaga C, Dalal S,. A possible linkage between AMP-activated protein kinase () and mammalian target of rapamycin (mtor) signalling pathway., 2003, 8(1): 65~79 [26] Horman S, Browne G, Krause U,. Activation of AMPactivated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis., 2002, 12(16): 1419~1423 [27] Horman S, Beauloye C, Vertommen D,. Myocardial ischemia and increased heart work modulate the phosphorylation state of eukaryotic elongation factor-2., 2003, 278(43): 41970~41976 [28] Yang W, Hong Y H, Shen X Q,. Regulation of transcription by AMP-activated protein kinase: phosphorylation of p300 blocks its interaction with nuclear receptors., 2001, 276(42): 38341~38344 [29] Lee M, Hwang J T, Lee H J,. AMP-activated protein kinase activity is critical for hypoxia-inducible factor-1 transcriptional activity and its target gene expression under hypoxic conditions in DU145 cells., 2003, 278(41): 39653~39661 [30] Hong Y H, Varanasi U S, Yang W,. AMP-activated protein kinase regulates transcriptional activity by inhibiting dimer formation and decreasing protein stability., 2003, 278(30): 27495~27501 [31] Al-Khalili L, Chibalin A V, Yu M,. MEF2 activation in differentiated primary human skeletal muscle cultures requires coordinated involvement of parallel pathways., 2004, 286(6): C1410~C1416 [32] Terada S, Tabata I. Effects of acute bouts of running and swimming exercise on PGC-1α protein expression in rat epitrochlearis and soleus muscle., 2004, 286(2): E208~E216

6 152 [33] Diraison F, Parton L, Ferre P,. Over-expression of sterolregulatory-element-binding protein-1c (SREBP1c) in rat pancreatic islets induces lipogenesis and decreases glucosestimulated insulin release: modulation by 5-aminoimidazole- 4-carboxamide ribonucleoside (AICAR)., 2004, 378(Pt 3): 769~778 [34] Kawaguchi T, Osatomi K, Yamashita H,. Mechanism for fatty acid paring effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase., 2002, 277(6): 3829~3835 [35] Kefas B A, Cai Y, Ling Z,. AMP-activated protein kinase can induce apoptosis of insulin-producing MIN6 cells through stimulation of c-jun-n-terminal kinase., 2003, 30(2): 151~161 [36] Van de Casteele M, Kefas B A, Cai Y,. Prolonged culture in low glucose induces apoptosis of rat pancreatic β-cells through induction of c-myc., 2003, 312(4): 937~944 [37] Garcia-Gil M, Pesi R, Perna S,. 5'-aminoimidazole-4- carboxamide riboside induces apoptosis in human neuroblastoma cells., 2003, 117(4): 811~820 [38] Jung J E, Lee J, Ha J,. 5-Aminoimidazole-4-carboxamideribonucleoside enhances oxidative stress-induced apoptosis through activation of nuclear factor-κb in mouse Neuro 2a neuroblastoma cells., 2004, 354(3): 197~200 [39] Nagata D, Mogi M, Walsh K,. AMP-activated protein kinase () signaling in endothelial cells is essential for angiogenesis in response to hypoxic stress., 2003, 278(33): 31000~31006 [40] Chen Z P, Mitchelhill K I, Michell B J,. AMP-activated protein kinase phosphorylation of endothelial NO synthase., 1999, 443(3): 285~289 [41] Morrow V A, Foufelle F, Connell J M,. Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells., 2003, 278(34): 31629~31639 [42] Walker J, Jijon H B, Churchill T,. Activation of AMPactivated protein kinase reduces camp-mediated epithelial chloride secretion., 2003, 285(5): G850~G860 [43] Giri S, Nath N, Smith B,. 5-aminoimidazole-4-carboxamide- 1-β-4-ribofuranoside inhibits proinflammatory response in glial cells: a possible role of AMP-activated protein kinase., 2004, 24(2): 479~487 [44] Pilon G, Dallaire P, Marette A,. Inhibition of inducible nitric-oxide synthase by activators of AMP-activated protein kinase: a new mechanism of action of insulin-sensitizing drugs., 2004, 279(20): 20767~20774 [45] Hallows K R, Raghuram V, Kemp B E,. Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP-activated protein kinase., 2000, 105(12): 1711~1721 [46] Light P E, Wallace C H, Dyck J R,. Constitutively active adenosine monophosphate-activated protein kinase regulates voltage-gated sodium channels in ventricular myocytes., 2003, 107(15): 1962~1965 [47] Andersson U, Filipsson K, Abbott C R,. AMP-activated protein kinase plays a role in the control of food intake., 2004, 279(13): 12005~12008 [48] Wang W, Yang X, Lopez de Silanes I,. Increased AMP: ratio and AMP-activated protein kinase activity during cellular senescence linked to reduced HuR function., 2003, 278(29): 27016~27023 [49] Zong H, Ren J M,Young L H,. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation., 2002, 99(25): 15983~15987 Karolinska Institutet 1 OX40L T