HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 98/1/296    most recent 00075.2004v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Rubin, L. J. Articles by Hale, C. C. Search for Related Content PubMed PubMed Citation Articles by Rubin, L. J. Articles by Hale, C. C.

Metabolic activation of AMP kinase in vascular smooth muscle

Departments of ¹Biomedical Sciences and ²Medical Pharmacology and Physiology, ³Dalton Cardiovascular Research Center, and Centers for ⁴Diabetes and Cardiovascular Health and ⁵Gender Physiology and Environmental Adaptations, University of Missouri, Columbia, Missouri

Submitted 22 January 2004 ; accepted in final form 10 September 2004

AMP-activated kinase (AMPK) is a highly conserved heterotrimeric kinase that functions as a metabolic master switch to coordinate cellular enzymes involved in carbohydrate and fat metabolism that regulate ATP conservation and synthesis. AMPK is activated by conditions that increase AMP-to-ATP ratio, such as exercise and metabolic stress. In the present study, we probed whether AMPK was expressed in vascular smooth muscle and would be activated by metabolic stress. Endothelium-denuded porcine carotid artery segments were metabolically challenged with 2-deoxyglucose (10 mM) plus N₂ (N₂-2DG). These vessels exhibited a rapid increase in AMPK activity by 1 min that was near maximal by 20 min. AMPK inactivation on return to normal physiological saline was 50% in 1 min and fully recovered by 5 min. Immunoprecipitation of the ₁- and ₂-catalytic subunit followed by immunoblot analysis for [P]Thr¹⁷²-AMPK indicates that ₁-AMPK accounts for all activity. Little if any ₂-AMPK was detected in carotid smooth muscle. AMPK activity was not increased by contractile agonist (endothelin-1) or by the reported AMPK activators 5-aminoimidazole-4-carboxamide ribofuranoside (2 mM), metformin (2 mM), or phenformin (0.2 mM). AMPK activation by N₂-2DG was associated with a rapid and pronounced reduction in endothelin-induced force and reduced phosphorylation of Akt and Erk 1/2. These data demonstrate that AMPK expression differs in vascular smooth muscle compared with striated muscles and that activation and inactivation after metabolic stress occur rapidly and are associated with signaling pathways that may regulate smooth-muscle contraction

porcine; carotid artery; 2-deoxyglucose; smooth muscle; adenosine 5'-monophosphate protein kinase

This article has been cited by other articles:

				M. Bendayan, I. Londono, B. E. Kemp, G. D. Hardie, N. Ruderman, and M. Prentki Association of AMP-activated Protein Kinase Subunits With Glycogen Particles as Revealed In Situ by Immunoelectron Microscopy J. Histochem. Cytochem., October 1, 2009; 57(10): 963 - 971. [Abstract] [Full Text] [PDF]

				B. Fisslthaler and I. Fleming Activation and Signaling by the AMP-Activated Protein Kinase in Endothelial Cells Circ. Res., July 17, 2009; 105(2): 114 - 127. [Abstract] [Full Text] [PDF]

				S. Horman, N. Morel, D. Vertommen, N. Hussain, D. Neumann, C. Beauloye, N. E. Najjar, C. Forcet, B. Viollet, M. P. Walsh, et al. AMP-activated Protein Kinase Phosphorylates and Desensitizes Smooth Muscle Myosin Light Chain Kinase J. Biol. Chem., July 4, 2008; 283(27): 18505 - 18512. [Abstract] [Full Text] [PDF]

				P. P. Dzeja, P. Bast, D. Pucar, B. Wieringa, and A. Terzic Defective Metabolic Signaling in Adenylate Kinase AK1 Gene Knock-out Hearts Compromises Post-ischemic Coronary Reflow J. Biol. Chem., October 26, 2007; 282(43): 31366 - 31372. [Abstract] [Full Text] [PDF]

				F. Goirand, M. Solar, Y. Athea, B. Viollet, P. Mateo, D. Fortin, J. Leclerc, J. Hoerter, R. Ventura-Clapier, and A. Garnier Activation of AMP kinase {alpha}1 subunit induces aortic vasorelaxation in mice J. Physiol., June 15, 2007; 581(3): 1163 - 1171. [Abstract] [Full Text] [PDF]

				M. A. Mayes, M. F. Laforest, C. Guillemette, R. B. Gilchrist, and F. J. Richard Adenosine 5'-Monophosphate Kinase-Activated Protein Kinase (PRKA) Activators Delay Meiotic Resumption in Porcine Oocytes Biol Reprod, April 1, 2007; 76(4): 589 - 597. [Abstract] [Full Text] [PDF]

				H.-J. Koh, D. E. Arnolds, N. Fujii, T. T. Tran, M. J. Rogers, N. Jessen, Y. Li, C. W. Liew, R. C. Ho, M. F. Hirshman, et al. Skeletal Muscle-Selective Knockout of LKB1 Increases Insulin Sensitivity, Improves Glucose Homeostasis, and Decreases TRB3 Mol. Cell. Biol., November 15, 2006; 26(22): 8217 - 8227. [Abstract] [Full Text] [PDF]

				K. Isoda, J. L. Young, A. Zirlik, L. A. MacFarlane, N. Tsuboi, N. Gerdes, U. Schonbeck, and P. Libby Metformin Inhibits Proinflammatory Responses and Nuclear Factor-{kappa}B in Human Vascular Wall Cells Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 611 - 617. [Abstract] [Full Text] [PDF]

				M. Igata, H. Motoshima, K. Tsuruzoe, K. Kojima, T. Matsumura, T. Kondo, T. Taguchi, K. Nakamaru, M. Yano, D. Kukidome, et al. Adenosine Monophosphate-Activated Protein Kinase Suppresses Vascular Smooth Muscle Cell Proliferation Through the Inhibition of Cell Cycle Progression Circ. Res., October 14, 2005; 97(8): 837 - 844. [Abstract] [Full Text] [PDF]

				R. Pullmann Jr., M. Juhaszova, I. L. de Silanes, T. Kawai, K. Mazan-Mamczarz, M. K. Halushka, and M. Gorospe Enhanced Proliferation of Cultured Human Vascular Smooth Muscle Cells Linked to Increased Function of RNA-binding Protein HuR J. Biol. Chem., June 17, 2005; 280(24): 22819 - 22826. [Abstract] [Full Text] [PDF]