Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte

Chan, Anita Y.M.; Soltys, Carrie-Lynn M.; Young, Martin E.; Proud, Christopher G.; Dyck, Jason R.B.

doi:10.1074/jbc.m403528200

Cited by 331Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerSignaling Pathways in Disease

Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte

Open access

Chan, Anita Y.M., Soltys, Carrie-Lynn M., Young, Martin E., Proud, Christopher G., Dyck, Jason R.B.·2004·Journal of Biological Chemistry

DOI 10.1074/jbc.m403528200

Open this paper in CoChat — free account

Abstract

A necessary mediator of cardiac myocyte enlargement is protein synthesis, which is controlled at the levels of both translation initiation and elongation. Eukaryotic elongation factor-2 (eEF2) mediates the translocation step of peptide-chain elongation and is inhibited through phosphorylation by eEF2 kinase. In addition, p70S6 kinase can regulate protein synthesis by phosphorylating eEF2 kinase or via phosphorylation of ribosomal protein S6. We have recently shown that eEF2 kinase is also controlled by phosphorylation by AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis. Moreover, the mammalian target of rapamycin has also been shown to be inhibited, indirectly, by AMPK, thus leading to the inhibition of p70S6 kinase. Although AMPK activation has been shown to modulate protein synthesis, it is unknown whether AMPK could also be a regulator of cardiac hypertrophic growth. Therefore, we investigated the role of AMPK activation in regulating protein synthesis during both phenylephrine- and Akt-induced cardiac hypertrophy. Metformin and 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside were used to activate AMPK in neonatal rat cardiac myocytes. Activation of AMPK significantly decreased protein synthesis induced by phenylephrine treatment or by expression of constitutively active Akt. Activation of AMPK also resulted in decreased p70S6 kinase phosphorylation and increased phosphorylation of eEF2, suggesting that inhibition of protein synthesis involves the eEF2 kinase/eEF2 axis and/or the p70S6 kinase pathway. Together, our data suggest that the inhibition of protein synthesis by pharmacological activation of AMPK may be a key regulatory mechanism by which hypertrophic growth can be controlled.

Integrity signals

Registry

Crossref · 10.1074/jbc.m403528200

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Loss of AMPK activity is pro-hypertrophic because lines of molecular signaling pathways that control cell growth are attenuated by AMPK activation.
“The loss of AMPK activity is believed to be pro-hypertrophic because lines of molecular signaling pathways that control cell growth are attenuated by AMPK activation [197,198,199].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [198]

Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · see citing works
Mechanism of activation of protein kinase B by insulin and IGF‐1.
Alessi, D. R., Andjelković, M., Caudwell, B., Cron, P. D., MORRICE, N. A., Cohen, P., & Hemmings, B. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01045.x · Cited by 2,985 · see citing works
A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy
Molkentin, J. D., Lu, J., Antos, C. L., Markham, B. E., Richardson, J. A., Robbins, J. M., Grant, S. R., & Olson, E. N. (1998) · Cell · doi:10.1016/s0092-8674(00)81573-1 · Cited by 2,566 · see citing works
Metformin
Bailey, C. J., & Turner, R. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602293340906 · Cited by 1,726 · see citing works
Cardiac Hypertrophy: The Good, the Bad, and the Ugly
Frey, N., & Olson, E. N. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142243 · Cited by 1,458 · see citing works
Left Ventricular Hypertrophy: Pathogenesis, Detection, and Prognosis
Lorell, B. H., & Carabello, B. A. (2000) · Circulation · doi:10.1161/01.cir.102.4.470 · Cited by 1,232 · see citing works
5-Aminoimidazole-4-Carboxamide Ribonucleoside. A Specific Method for Activating AMP-Activated Protein Kinase in Intact Cells?
Corton, J. M., Gillespie, J. G., Hawley, S. A., & Hardie, D. G. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20498.x · Cited by 1,232 · see citing works
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093 · see citing works
Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k
Jefferies, H. B. J., Fumagalli, S., Dennis, P. B., Reinhard, C., Pearson, R. B., & Thomas, G. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3693 · Cited by 934 · see citing works
Regulation of elongation factor 2 kinase by p90RSK1 and p70 S6 kinase
Wang, X.-M., Li, W., Williams, M. R., Terada, N., Alessi, D., & Proud, C. G. (2001) · EMBO Journal · doi:10.1093/emboj/20.16.4370 · Cited by 862 · see citing works
Self-citation
Akt Promotes Survival of Cardiomyocytes In Vitro and Protects Against Ischemia-Reperfusion Injury in Mouse Heart
Fujio, Y., Nguyen, T. U., Wencker, D., Kitsis, R. N., & Walsh, K. (2000) · Circulation · doi:10.1161/01.cir.101.6.660 · Cited by 846 · see citing works
The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism
Hawley, S. A., Gadalla, A. E., Olsen, G. S., & Hardie, D. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2420 · Cited by 696 · see citing works
Identification of a gene responsible for familial Wolff-Parkinson-White syndrome
Gollob, M. H., Green, M. S., Tang, A. S.-L., Gollob, T., Karibe, A., Hassan, A.-S., Ahmad, F., Lozado, R., Shah, G., Fananapazir, L., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200106143442403 · Cited by 671 · see citing works
The conserved phosphoinositide 3‐kinase pathway determines heart size in mice
Shioi, T., Kang, P., Douglas, P., Hampe, J., Yballe, C., Lawitts, J., Cantley, L., & Izumo, S. (2000) · EMBO Journal · doi:10.1093/emboj/19.11.2537 · Cited by 646 · see citing works
Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family.
Jefferies, H. B. J., Reinhard, C., Kozma, S. C., & Thomas, G. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4441 · Cited by 623 · see citing works
The regulation of AMP-activated protein kinase by phosphorylation
STEIN, S. C., Woods, A., Jones, N. A., DAVISON, M. D., & Carling, D. (2000) · Biochemical Journal · doi:10.1042/bj3450437 · Cited by 605 · see citing works
Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy
Arad, M., Benson, D. W., Pérez‐Atayde, A. R., McKenna, W. J., Sparks, E. A., Kanter, R. J., McGarry, K., Seidman, J. G., & Seidman, C. E. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14571 · Cited by 545 · see citing works
Akt/Protein Kinase B Promotes Organ Growth in Transgenic Mice
Shioi, T., McMullen, J., Kang, P., Douglas, P., Obata, T., Franke, T. F., Cantley, L., & Izumo, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.8.2799-2809.2002 · Cited by 544 · see citing works
Mutations in the gamma2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis
Blair, E. M. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.11.1215 · Cited by 531 · see citing works
Regulation of peptide‐chain elongation in mammalian cells
Browne, G. J., & Proud, C. G. (2002) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2002.03290.x · Cited by 469 · see citing works
Self-citation
The principal target of rapamycin‐induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain.
Pearson, R. B., Dennis, P. B., Han, J. W., Williamson, N. A., Kozma, S. C., Wettenhall, R. E., & Thomas, G. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00212.x · Cited by 443 · see citing works
Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis.
Horman, S., Browne, G., Krause, U., Patel, J., Vertommen, D., Bertrand, L., Lavoinne, A., Hue, L., Proud, C. G., & Rider, M. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01077-1 · Cited by 440 · see citing works
Self-citation
Phenotypic Spectrum Caused by Transgenic Overexpression of Activated Akt in the Heart
Matsui, T., Li, L., Wu, J. C., Cook, S. A., Nagoshi, T., Picard, M. H., Liao, R., & Rosenzweig, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200347200 · Cited by 434 · see citing works
Role of the AMP-activated protein kinase in the cellular stress response
Corton, J. M., Gillespie, J. G., & Hardie, D. G. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00070-1 · Cited by 423 · see citing works
Akt Activity Negatively Regulates Phosphorylation of AMP-activated Protein Kinase in the Heart
Kovacic, S., Soltys, C.-L. M., Barr, A., Shiojima, I., Walsh, K., & Dyck, J. R. B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305371200 · Cited by 407 · see citing works
Self-citation
Cellular mechanisms of cardiac hypertrophy
Sugden, P. H., & Clerk, A. (1998) · Journal of Molecular Medicine · doi:10.1007/s001090050275 · Cited by 404 · see citing works
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
Browne, G. J., Finn, S. G., & Proud, C. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309773200 · Cited by 353 · see citing works
Identification of the major Mr 100,000 substrate for calmodulin-dependent protein kinase III in mammalian cells as elongation factor-2.
Nairn, A. C., & Palfrey, H. C. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45377-x · Cited by 341 · see citing works
Immunopurified Mammalian Target of Rapamycin Phosphorylates and Activates p70 S6 Kinase α in Vitro
Isotani, S., Hara, K., Tokunaga, C., Inoue, H., Avruch, J., & Yonezawa, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.48.34493 · Cited by 337 · see citing works
Thr2446 Is a Novel Mammalian Target of Rapamycin (mTOR) Phosphorylation Site Regulated by Nutrient Status
Cheng, S., Fryer, L. G. D., Carling, D., & Shepherd, P. R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300534200 · Cited by 328 · see citing works
Transgenic Mice Overexpressing Mutant PRKAG2 Define the Cause of Wolff-Parkinson-White Syndrome in Glycogen Storage Cardiomyopathy
Arad, M., Moskowitz, I. P. G., Patel, V. V., Ahmad, F., Pérez‐Atayde, A. R., Sawyer, D. B., Walter, M., Li, G. H., Burgon, P. G., Maguire, C. T., et al. (2003) · Circulation · doi:10.1161/01.cir.0000075270.13497.2b · Cited by 323 · see citing works
Increased Adenosine Monophosphate–Activated Protein Kinase Activity in Rat Hearts With Pressure-Overload Hypertrophy
Tian, R., Musi, N., D’Agostino, J., Hirshman, M. F., & Goodyear, L. J. (2001) · Circulation · doi:10.1161/hc4001.097183 · Cited by 308 · see citing works
The alpha 1A-adrenergic receptor subtype mediates biochemical, molecular, and morphologic features of cultured myocardial cell hypertrophy
Knowlton, K. U., Michel, M. C., Itani, M., Shubeita, H. E., Ishihara, K., Brown, J. H., & Chien, K. R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82267-0 · Cited by 301 · see citing works
Functional properties of phosphorylated elongation factor 2
CARLBERG, U., NILSSON, A., & Nygârd, O. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb19169.x · Cited by 287 · see citing works
Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase
DAVIES, S. P., SIM, A. T. R., & HARDIE, D. G. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb15293.x · Cited by 274 · see citing works
A Novel mTOR-Regulated Phosphorylation Site in Elongation Factor 2 Kinase Modulates the Activity of the Kinase and Its Binding to Calmodulin
Browne, G. J., & Proud, C. G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.7.2986-2997.2004 · Cited by 256 · see citing works
Self-citation
The Principal Rapamycin-Sensitive p70s6k Phosphorylation Sites, T-229 and T-389, Are Differentially Regulated by Rapamycin-Insensitive Kinase Kinases
Dennis, P. B., Pullen, N., Kozma, S. C., & Thomas, G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.6242 · Cited by 249 · see citing works
Characterization of AMP-activated Protein Kinase β and γ Subunits
Woods, A., Cheung, P., Smith, F. C., Davison, M. D., Scott, J., Beri, R. K., & Carling, D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.17.10282 · Cited by 243 · see citing works
Akt Signaling Mediates Postnatal Heart Growth in Response to Insulin and Nutritional Status
Shiojima, I., Yefremashvili, M., Luo, Z., Kureishi, Y., Takahashi, A., Tao, J., Rosenzweig, A., Kahn, C. R., Abel, E. D., & Walsh, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204572200 · Cited by 220 · see citing works
mTOR-mediated regulation of translation factors by amino acids
Proud, C. G. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.07.015 · Cited by 205 · see citing works
Self-citation
p70 S6 kinase: an enigma with variations
Proud, C. G. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10016-5 · Cited by 201 · see citing works
Self-citation
Insulin-like Growth Factor-I Rapidly Activates Multiple Signal Transduction Pathways in Cultured Rat Cardiac Myocytes
Foncea, R. E., Andersson, M., Ketterman, A. J., Blakesley, V. A., Sapag-Hagar, M., Sugden, P. H., LeRoith, D., & Lavandero, S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19115 · Cited by 198 · see citing works
Regulation of elongation factor‐2 by multisite phosphorylation
Redpath, N. T., Price, N. T., Severinov, K., et al. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb17809.x · Cited by 182 · see citing works
Gene Regulatory Mechanisms Governing Energy Metabolism during Cardiac Hypertrophic Growth
Lehman, J. J., & Kelly, D. P. (2002) · Heart Failure Reviews · doi:10.1023/a:1015332726303 · Cited by 169 · see citing works
Cardiac hypertrophy: A matter of translation
Hannan, R. D., Jenkins, A., Jenkins, A., & Brandenburger, Y. (2003) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.2003.03873.x · Cited by 150 · see citing works
Cross-talk between the ERK and p70 S6 Kinase (S6K) Signaling Pathways
Wang, L., Gout, I. T., & Proud, C. G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102776200 · Cited by 130 · see citing works
Self-citation
Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase.
Stapleton, D., Gao, G., Michell, B. J., Widmer, J., Mitchelhill, K. I., Teh, T., House, C. M., Witters, L. A., & Kemp, B. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43879-3 · Cited by 122 · see citing works
Functional Analysis of Mutations in the γ2 Subunit of AMP-activated Protein Kinase Associated with Cardiac Hypertrophy and Wolff-Parkinson-White Syndrome
Daniel, T. D., & Carling, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207093200 · Cited by 121 · see citing works
Myocardial Ischemia and Increased Heart Work Modulate the Phosphorylation State of Eukaryotic Elongation Factor-2
Horman, S., Beauloye, C., Vertommen, D., Vanoverschelde, J., Hue, L., & Rider, M. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302403200 · Cited by 121 · see citing works
Pathological versus physiological left ventricular hypertrophy: A review
Richey, P. A., & Brown, S. P. (1998) · Journal of Sports Sciences · doi:10.1080/026404198366849 · Cited by 106 · see citing works
Acadesine: the prototype adenosine regulating agent for reducing myocardial ischaemic injury
Mullane, K. (1993) · Cardiovascular Research · doi:10.1093/cvr/27.1.43 · Cited by 84 · see citing works
Stress-induced regulation of eukaryotic elongation factor 2 kinase by SB 203580-sensitive and −insensitive pathways
Knebel, A., Haydon, C. E., MORRICE, N. A., & Cohen, P. (2002) · Biochemical Journal · doi:10.1042/bj20020916 · Cited by 80 · see citing works
Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity
Diggle, T. A., Subkhankulova, T., Lilley, K. S., SHIKOTRA, N., Willis, A. E., & Redpath, N. T. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3530621 · Cited by 77 · see citing works
Mammalian Target of Rapamycin and Protein Kinase A Signaling Mediate the Cardiac Transcriptional Response to Glutamine*
Xia, Y., Wen, H., Young, M., Guthrie, P. H., Taegtmeyer, H., & Kellems, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208500200 · Cited by 69 · see citing works
Self-citation
Regulation of the phosphorylation of elongation factor 2 by MEK‐dependent signalling in adult rat cardiomyocytes
Wang, L., & Proud, C. G. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03536-6 · Cited by 59 · see citing works
Self-citation
Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity
Diggle, T. A., Subkhankulova, T., Lilley, K. S., et al. (2001) · Biochemical Journal · doi:10.1042/bj3530621 · Cited by 56 · see citing works
TSH signaling and cell survival in 3T3-L1 preadipocytes.
Bell, A., Gagnon, A., Dods, P. L., Papineau, D., Tiberi, M., & Sorisky, A. (2002) · American Journal of Physiology - Cell Physiology · doi:10.1152/ajpcell.00058.2002 · Cited by 45 · see citing works

Flagged first, then by citations

Sorted by citations

Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells
Dowling, R. J. O., Zakikhani, M., Fantus, I. G., Pollak, M., & Sonenberg, N. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2310 · Cited by 933 · see citing works
Adiponectin-mediated modulation of hypertrophic signals in the heart
Shibata, R., Ouchi, N., Ito, M., Kihara, S., Shiojima, I., Pimentel, D. R., Kumada, M., Sato, K., Schiekofer, S., Ohashi, K., et al. (2004) · Nature Medicine · doi:10.1038/nm1137 · Cited by 671 · see citing works
LKB1 and AMP-activated protein kinase control of mTOR signalling and growth
Shaw, R. J. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.01972.x · Cited by 644 · see citing works
Adiponectin regulation and function
Fang, H., & Judd, R. L. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170046 · Cited by 631 · see citing works
AMPK: Lessons from transgenic and knockout animals
Viollet, B. (2009) · Frontiers in bioscience · doi:10.2741/3229 · Cited by 314 · see citing works
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
AMP-activated protein kinase regulation and biological actions in the heart
Zaha, V. G., & Young, L. H. (2012) · Circulation Research · doi:10.1161/circresaha.111.255505 · Cited by 279 · see citing works
The Cardiomyocyte Circadian Clock: Emerging Roles in Health and Disease
Durgan, D. J., & Young, M. E. (2010) · Circulation Research · doi:10.1161/circresaha.109.209957 · Cited by 277 · see citing works
Self-citation
The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration
Thomson, D. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103125 · Cited by 267 · see citing works
Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise
Jørgensen, S. B., Richter, E. A., & Wojtaszewski, J. F. P. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109942 · Cited by 261 · see citing works
The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse
White, J. P., Baynes, J. W., Welle, S. L., Kostek, M. C., Matesic, L. E., Sato, S., & Carson, J. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024650 · Cited by 260 · see citing works
“Muscle 59adenosine monophosphate-activated protein kinase (AMPK), a sensor of cellular energy status, also regulates protein synthesis [19,20,21].”
Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt
Chan, A. Y. M., Dolinsky, V. W., Soltys, C.-L. M., Viollet, B., Baksh, S., Light, P. E., & Dyck, J. R. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802869200 · Cited by 244 · see citing works
Self-citation
Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle
Glund, S., Deshmukh, A., Long, Y. C., Moller, T., Koistinen, H. A., Caidahl, K., Zierath, J. R., & Krook, A. (2007) · Diabetes · doi:10.2337/db06-1733 · Cited by 219 · see citing works
Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunction
Ikeda, Y., Sato, K., Pimentel, D. R., Sam, F., Shaw, R. J., Dyck, J. R. B., & Walsh, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.057273 · Cited by 164 · see citing works
Self-citation
Influence of muscle glycogen availability on ERK1/2 and Akt signaling after resistance exercise in human skeletal muscle
Creer, A., Gallagher, P., Slivka, D., Jemiolo, B., Fink, W., & Trappe, S. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00110.2005 · Cited by 150 · see citing works
AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunction
Turdi, S., Fan, X., Li, J., Zhao, J., Huff, A. F., Du, M., & Ren, J. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00586.x · Cited by 141 · see citing works
Important role for AMPKαl in limiting skeletal muscle cell hypertrophy
Mounier, R., Lantier, L., Leclerc, J., Sotiropoulos, A., Pende, M., Daegelen, D., Sakamoto, K., Foretz, M., & Viollet, B. (2009) · The FASEB Journal · doi:10.1096/fj.08-119057 · Cited by 133 · see citing works
Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation
Thomson, D. M., & Gordon, S. E. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00811.2004 · Cited by 131 · see citing works
Insulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training
Riehle, C., Wende, A. R., Zhu, Y., Oliveira, K. J., Pereira, R. O., Jaishy, B. P., Bevins, J., Valdez, S., Noh, J., Kim, B. J., et al. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00426-14 · Cited by 105 · see citing works
Metformin treatment in heart failure with preserved ejection fraction: A systematic review and meta-regression analysis
Halabi, A., Sen, J., Huynh, Q., & Marwick, T. H. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01100-w · Cited by 93 · see citing works
Thromboxane receptor activates the AMP-activated protein kinase in vascular smooth muscle cells via hydrogen peroxide
Zhang, M., Dong, Y., Xu, J., Xie, Z., Wu, Y., Song, P., Guzman, M., Wu, J., & Zou, M.-H. (2008) · Circulation Research · doi:10.1161/circresaha.107.163253 · Cited by 82 · see citing works
AMP-activated protein kinase conducts the ischemic stress response orchestra
Young, L. H. (2008) · Circulation · doi:10.1161/circulationaha.107.713115 · Cited by 82 · see citing works
Estrogen‐related receptor‐α (ERRα) deficiency in skeletal muscle impairs regeneration in response to injury
LaBarge, S., McDonald, M., Smith‐Powell, L., Auwerx, J., & Huss, J. M. (2014) · The FASEB Journal · doi:10.1096/fj.13-229211 · Cited by 74 · see citing works
Insulin signalling downstream of protein kinase B is potentiated by 5′AMP-activated protein kinase in rat hearts in vivo
Longnus, S. L., Ségalen, C., Giudicelli, J., Sajan, M. P., Farese, R. V., & Van Obberghen, E. (2005) · Diabetologia · doi:10.1007/s00125-005-0016-3 · Cited by 58 · see citing works
AMP-activated kinase may suppress NADPH oxidase activation in vascular tissues
McCarty, M. F., Barroso-Aranda, J., & Contreras, F. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2008.12.024 · Cited by 22 · see citing works

Mitogen-Independent Phosphorylation of S6K1 and Decreased Ribosomal S6 Phosphorylation in Senescent Human Fibroblasts
Zhang, H., Hoff, H. B., Marinucci, T., Cristofalo, V. J., & Sell, C. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4965 · Cited by 29 · see citing works
Rapamycin-Sensitive Phosphorylation of Ribosomal Protein S17 by p70 S6 Kinase
Patel, H. R., Terada, N., & Gelfand, E. W. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1537 · Cited by 15 · see citing works
Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)
Pearce, L. R., Alton, G., Richter, D. T., Kath, J. C., Lingardo, L., Chapman, J., Hwang, C., & Alessi, D. R. (2010) · Biochemical Journal · doi:10.1042/bj20101024 · Cited by 267 · see citing works
Faculty Opinions recommendation of Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1).
Toker, A. (2010) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.5714957.5695055
Branched-Chain Amino Acids Activate Key Enzymes in Protein Synthesis after Physical Exercise
Blomstrand, E., Eliasson, J., Karlsson, H. K., & Köhnke, R. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.1.269s · Cited by 395 · see citing works

Authors: Chan, A. Y. M., Soltys, C.-L. M., Young, M. E., Proud, C. G., & Dyck, J. R. B.
Affiliations: University of Alberta (CA)
Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
University of Dundee (GB)
Corresponding author: Dyck, Jason R.B.
ORCID: Soltys, Carrie-Lynn M.
Young, Martin E.
Proud, Christopher G.
Dyck, Jason R.B.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2004-07
Volume: 279
Issue: 31
Pages: 32771-32779
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m403528200
OpenAlex: W2087766892
Cited by: 331
References: 58
Citations by year: 2026: 5 · 2025: 8 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 14 · 2020: 14 · 2019: 12 · 2018: 17 · 2017: 20 · 2016: 11 · 2015: 15 · 2014: 21 · 2013: 19 · 2012: 16
FWCI: 5.45
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5929 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: AMPK, cardiac hypertrophy, protein synthesis, elongation factor 2, eEF2 kinase, p70 S6 kinase, ribosomal protein S6, translation elongation, Akt, phenylephrine, metformin, AICAR, cardiomyocytes, energy homeostasis
MeSH terms: Aminoimidazole Carboxamide, Animals, Animals, Newborn, Antibiotics, Antineoplastic, Cells, Cultured, Enzyme Activation, Hypertrophy, Hypoglycemic Agents, Luminescent Proteins, Metformin, Microscopy, Fluorescence, Multienzyme Complexes, Phenylephrine, Phosphorylation, Ribonucleotides, Ribose, Time Factors, Immunoblotting, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Sirolimus, Myocytes, Cardiac, Ribosomal Protein S6, Ribosomal Protein S6 Kinases, 70-kDa, Green Fluorescent Proteins, Rats, Elongation Factor 2 Kinase, AMP-Activated Protein Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks