AMPK signalling in health and disease

被引:608
作者
Carling, David [1 ]
机构
[1] Imperial Coll, Hammersmith Hosp, MRC London Inst Med Sci, London W12 0NN, England
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
ACTIVATED PROTEIN-KINASE; PARKINSON-WHITE-SYNDROME; GAMMA-SUBUNIT ISOFORMS; SKELETAL-MUSCLE; HYPERTROPHIC CARDIOMYOPATHY; STRUCTURAL BASIS; UPSTREAM KINASE; VENTRICULAR PREEXCITATION; CARDIAC-HYPERTROPHY; MUTATION;
D O I
10.1016/j.ceb.2017.01.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In eukaryotic cells AMP-activated protein kinase (AMPK) plays a major role in regulating cellular energy balance. AMPK responds to changes in intracellular adenine nucleotide levels, being activated by an increase in AMP/ADP relative to ATP. Activation of AMPK increases the rate of catabolic (ATP-generating) pathways and decreases the rate of anabolic (ATP-utilising) pathways. In addition to its role in maintaining intracellular energy balance, AMPK regulates whole body energy metabolism. Given its key role in controlling energy homeostasis, AMPK has attracted widespread interest as a potential therapeutic target for metabolic diseases, including type 2 diabetes and, more recently, cancer. Here I review the regulation of AMPK and its potential as a target for therapeutic intervention in human disease.
引用
收藏
页码:31 / 37
页数:7
相关论文
共 51 条
[1]   Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy [J].
Arad, M ;
Moskowitz, IP ;
Patel, VV ;
Ahmad, F ;
Perez-Atayde, AR ;
Sawyer, DB ;
Walter, M ;
Li, GH ;
Burgon, PG ;
Maguire, CT ;
Stapleton, D ;
Schmitt, JP ;
Guo, XX ;
Pizard, A ;
Kupershmidt, S ;
Roden, DM ;
Berul, CI ;
Seidman, CE ;
Seidman, JG .
CIRCULATION, 2003, 107 (22) :2850-2856
[2]   Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy [J].
Arad, M ;
Benson, DW ;
Perez-Atayde, AR ;
McKenna, WJ ;
Sparks, EA ;
Kanter, RJ ;
McGarry, K ;
Seidman, JG ;
Seidman, CE .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (03) :357-362
[3]   Mutations in the γ2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy:: evidence for the central role of energy compromise in disease pathogenesis [J].
Blair, E ;
Redwood, C ;
Ashrafian, H ;
Oliveira, M ;
Broxholme, J ;
Kerr, B ;
Salmon, A ;
Östman-Smith, I ;
Watkins, H .
HUMAN MOLECULAR GENETICS, 2001, 10 (11) :1215-1220
[4]   OXIDATIVE-PHOSPHORYLATION AND PHOTOPHOSPHORYLATION [J].
BOYER, PD ;
CHANCE, B ;
ERNSTER, L ;
MITCHELL, P ;
RACKER, E ;
SLATER, EC .
ANNUAL REVIEW OF BIOCHEMISTRY, 1977, 46 :955-1026
[5]   Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle [J].
Bultot, Laurent ;
Jensen, Thomas E. ;
Lai, Yu-Chiang ;
Madsen, Agnete L. B. ;
Collodet, Caterina ;
Kviklyte, Samanta ;
Deak, Maria ;
Yavari, Arash ;
Foretz, Marc ;
Ghaffari, Sahar ;
Bellahcene, Mohamed ;
Ashrafian, Houman ;
Rider, Mark H. ;
Richter, Erik A. ;
Sakamoto, Kei .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2016, 311 (04) :E706-E719
[6]   Structural Basis for AMPK Activation: Natural and Synthetic Ligands Regulate Kinase Activity from Opposite Poles by Different Molecular Mechanisms [J].
Calabrese, Matthew F. ;
Rajamohan, Francis ;
Harris, Melissa S. ;
Caspers, Nicole L. ;
Magyar, Rachelle ;
Withka, Jane M. ;
Wang, Hong ;
Borzilleri, Kris A. ;
Sahasrabudhe, Parag V. ;
Hoth, Lise R. ;
Geoghegan, Kieran F. ;
Han, Seungil ;
Brown, Janice ;
Subashi, Timothy A. ;
Reyes, Allan R. ;
Frisbie, Richard K. ;
Ward, Jessica ;
Miller, Russell A. ;
Landro, James A. ;
Londregan, Allyn T. ;
Carpino, Philip A. ;
Cabral, Shawn ;
Smith, Aaron C. ;
Conn, Edward L. ;
Cameron, Kimberly O. ;
Qiu, Xiayang ;
Kurumbail, Ravi G. .
STRUCTURE, 2014, 22 (08) :1161-1172
[7]   Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy [J].
Cameron, Kimberly O. ;
Kung, Daniel W. ;
Kalgutkar, Amit S. ;
Kurumbail, Ravi G. ;
Miller, Russell ;
Salatto, Christopher T. ;
Ward, Jessica ;
Withka, Jane M. ;
Bhattacharya, Samit K. ;
Boehm, Markus ;
Borzilleri, Kris A. ;
Brown, Janice A. ;
Calabrese, Matthew ;
Caspers, Nicole L. ;
Cokorinos, Emily ;
Conn, Edward L. ;
Dowling, Matthew S. ;
Edmonds, David J. ;
Eng, Heather ;
Fernando, Dilinie P. ;
Frisbie, Richard ;
Hepworth, David ;
Landro, James ;
Mao, Yuxia ;
Rajamohan, Francis ;
Reyes, Allan R. ;
Rose, Colin R. ;
Ryder, Tim ;
Shavnya, Andre ;
Smith, Aaron C. ;
Tu, Meihua ;
Wolford, Angela C. ;
Xiao, Jun .
JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (17) :8068-8081
[8]   AMP-activated protein kinase: new regulation, new roles? [J].
Carling, David ;
Thornton, Claire ;
Woods, Angela ;
Sanders, Matthew J. .
BIOCHEMICAL JOURNAL, 2012, 445 :11-27
[9]  
Carling D, 2011, NAT CHEM BIOL, V7, P512, DOI [10.1038/NCHEMBIO.610, 10.1038/nchembio.610]
[10]   Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding [J].
Cheung, PCF ;
Salt, IP ;
Davies, SP ;
Hardie, DG ;
Carling, D .
BIOCHEMICAL JOURNAL, 2000, 346 :659-669