| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Human Physiology, Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen; 2Department of Molecular Muscle Biology, Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen; and 3Department of Medical Biochemistry and Genetics, Medical Muscle Research Cluster, Molecular Muscle Biology, University of Copenhagen, Copenhagen, Denmark
Submitted 29 August 2006 ; accepted in final form 8 January 2007
The Ca2+/calmodulin (CaM) competitive inhibitor KN-93 has previously been used to evaluate 5'-AMP-activated protein kinase (AMPK)-independent Ca2+-signaling to contraction-stimulated glucose uptake in muscle during intense electrical stimulation ex vivo. With the use of low-intensity tetanic contraction of mouse soleus and extensor digitorum longus (EDL) muscles ex vivo, this study demonstrates that KN-93 can potently inhibit AMPK phosphorylation and activity after 2 min but not 10 min of contraction while strongly inhibiting contraction-stimulated 2-deoxyglucose uptake at both the 2- and 10-min time points. These data suggest inhibition of Ca2+/CaM-dependent signaling events upstream of AMPK, the most likely candidate being the novel AMPK kinase CaM-dependent protein kinase kinase (CaMKK). CaMKK protein expression was detected in mouse skeletal muscle. Similar to KN-93, the CaMKK inhibitor STO-609 strongly reduced AMPK phosphorylation and activity at 2 min and less potently at 10 min. Pretreatment with STO-609 inhibited contraction-stimulated glucose uptake at 2 min in soleus, but not EDL, and in both muscles after 10 min. Neither KN-93 nor STO-609 inhibited 5-aminoimidazole-4-carboxamide-1-
-4-ribofuranoside-stimulated glucose uptake, AMPK phosphorylation, or recombinant LKB1 activity, suggestive of an LKB1-independent effect. Finally, neither KN-93 nor STO-609 had effects on the reductions in glucose uptake seen in mice overexpressing a kinase-dead AMPK construct, indicating that the effects of KN-93 and STO-609 on glucose uptake require inhibition of AMPK activity. We propose that CaMKKs act in mouse skeletal muscle regulating AMPK phosphorylation and glucose uptake at the onset of mild tetanic contraction and that an intensity- and/or time-dependent switch occurs in the relative importance of AMPKKs during contraction.
KN-93; STO-609; calmodulin kinase kinase
This article has been cited by other articles:
|
|
 |
|
  M. J. Abbott, A. M. Edelman, and L. P. Turcotte CaMKK is an upstream signal of AMP-activated protein kinase in regulation of substrate metabolism in contracting skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1724 - R1732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Deshmukh, S. Glund, R. Z. Tom, and J. R. Zierath Role of the AMPK{gamma}3 isoform in hypoxia-stimulated glucose transport in glycolytic skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2009; 297(6): E1388 - E1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Maarbjerg, S. B. Jorgensen, A. J. Rose, J. Jeppesen, T. E. Jensen, J. T. Treebak, J. B. Birk, P. Schjerling, J. F. P. Wojtaszewski, and E. A. Richter Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice Am J Physiol Endocrinol Metab, October 1, 2009; 297(4): E924 - E934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kewalramani, P. Puthanveetil, F. Wang, M. S. Kim, S. Deppe, A. Abrahani, D. S. Luciani, J. D. Johnson, and B. Rodrigues AMP-activated protein kinase confers protection against TNF-{alpha}-induced cardiac cell death Cardiovasc Res, October 1, 2009; 84(1): 42 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pehmoller, J. T. Treebak, J. B. Birk, S. Chen, C. MacKintosh, D. G. Hardie, E. A. Richter, and J. F. P. Wojtaszewski Genetic disruption of AMPK signaling abolishes both contraction- and insulin-stimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E665 - E675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Murgia, T. E. Jensen, M. Cusinato, M. Garcia, E. A. Richter, and S. Schiaffino Multiple signalling pathways redundantly control glucose transporter GLUT4 gene transcription in skeletal muscle J. Physiol., September 1, 2009; 587(17): 4319 - 4327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhou, S. S. Deepa, J. C. Etzler, J. Ryu, X. Mao, Q. Fang, D. D. Liu, J. M. Torres, W. Jia, J. D. Lechleiter, et al. Adiponectin Activates AMP-activated Protein Kinase in Muscle Cells via APPL1/LKB1-dependent and Phospholipase C/Ca2+/Ca2+/Calmodulin-dependent Protein Kinase Kinase-dependent Pathways J. Biol. Chem., August 14, 2009; 284(33): 22426 - 22435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Jensen, S. J. Maarbjerg, A. J. Rose, M. Leitges, and E. A. Richter Knockout of the predominant conventional PKC isoform, PKC{alpha}, in mouse skeletal muscle does not affect contraction-stimulated glucose uptake Am J Physiol Endocrinol Metab, August 1, 2009; 297(2): E340 - E348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Steinberg and B. E. Kemp AMPK in Health and Disease Physiol Rev, July 1, 2009; 89(3): 1025 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Bilan and J. D. Schertzer Brought in by force: AMPK, TBC1D1, and contraction-stimulated glucose transport in skeletal muscle Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E965 - E966. [Full Text] [PDF]
|
|
|
|
|
|
D.M. Thomson, J.D. Brown, N. Fillmore, S.K. Ellsworth, D. L. Jacobs, W.W. Winder, C.A. Fick, and S.E. Gordon AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle J. Physiol., May 1, 2009; 587(9): 2077 - 2086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Rose, T. J. Alsted, T. E. Jensen, J. B. Kobbero, S. J. Maarbjerg, J. Jensen, and E. A. Richter A Ca2+-calmodulin-eEF2K-eEF2 signalling cascade, but not AMPK, contributes to the suppression of skeletal muscle protein synthesis during contractions J. Physiol., April 1, 2009; 587(7): 1547 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Weisova, C. G. Concannon, M. Devocelle, J. H. M. Prehn, and M. W. Ward Regulation of Glucose Transporter 3 Surface Expression by the AMP-Activated Protein Kinase Mediates Tolerance to Glutamate Excitation in Neurons J. Neurosci., March 4, 2009; 29(9): 2997 - 3008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lefort, E. St.-Amand, S. Morasse, C. H. Cote, and A. Marette The {alpha}-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1447 - E1454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Branvold, D. R. Allred, D. J. Beckstead, H. J. Kim, N. Fillmore, B. M. Condon, J. D. Brown, S. N. Sudweeks, D. M. Thomson, and W. W. Winder Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1{alpha} in rat muscle J Appl Physiol, October 1, 2008; 105(4): 1218 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. H. Smith, T. A. Kohn, A. K. Chetty, and E. O. Ojuka CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E698 - E704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ljubicic and D. A. Hood Kinase-specific responsiveness to incremental contractile activity in skeletal muscle with low and high mitochondrial content Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E195 - E204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Raney and L. P. Turcotte Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle J Appl Physiol, May 1, 2008; 104(5): 1366 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. McGee, K. J. Mustard, D. G. Hardie, and K. Baar Normal hypertrophy accompanied by phosphoryation and activation of AMP-activated protein kinase {alpha}1 following overload in LKB1 knockout mice J. Physiol., March 15, 2008; 586(6): 1731 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Thomson, C. A. Fick, and S. E. Gordon AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions J Appl Physiol, March 1, 2008; 104(3): 625 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Kristensen, A. B. Johnsen, J. B. Birk, J. N. Nielsen, B. R. Jensen, Y. Hellsten, E. A. Richter, and J. F. P. Wojtaszewski Absence of humoral mediated 5'AMP-activated protein kinase activation in human skeletal muscle and adipose tissue during exercise J. Physiol., December 15, 2007; 585(3): 897 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. W. Shen, M. J. Zhu, J. Tong, J. Ren, and M. Du Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by {alpha}-lipoic acid in C2C12 myotubes Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1395 - C1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Weigert, M. Dufer, P. Simon, E. Debre, H. Runge, K. Brodbeck, H. U. Haring, and E. D. Schleicher Upregulation of IL-6 mRNA by IL-6 in skeletal muscle cells: role of IL-6 mRNA stabilization and Ca2+-dependent mechanisms Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1139 - C1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Jensen, A. J. Rose, Y. Hellsten, J. F. P. Wojtaszewski, and E. A. Richter Caffeine-induced Ca2+ release increases AMPK-dependent glucose uptake in rodent soleus muscle Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E286 - E292. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
