Ablation of LKB1 in the heart leads to energy deprivation and impaired cardiac function

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1802, Issue 7-8, 2010, Pages 593-600

  Jessen, Niels ^a,b   Koh, Ho Jin ^a   Folmes, Clifford D ^c   Wagg, Cory ^c   Fujii, Nobuharu ^a   Løfgren, Bo ^a   Wolf, Cordula M ^d   Berul, Charles I ^d   Hirshman, Michael F ^a   Lopaschuk, Gary D ^c   Goodyear, Laurie J ^a  

^a JOSLIN DIABETES CENTER   (United States)

^b AARHUS UNIVERSITY   (Denmark)

^c UNIVERSITY OF ALBERTA   (Canada)

^d BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

AMP activated protein kinase; Cardiac function; LKB1; MTOR

Indexed keywords

ADENOSINE PHOSPHATE; ADENOSINE TRIPHOSPHATE; CRE RECOMBINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; LOX PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MEMBRANE PROTEIN; PROTEIN KINASE LKB1; UNCLASSIFIED DRUG;

AEROBIC CAPACITY; AEROBIC METABOLISM; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENERGY; ENERGY DEPRIVATION; EX VIVO STUDY; HEART FUNCTION; HEART MUSCLE CELL; HEART MUSCLE ISCHEMIA; HEART PERFUSION; HEART RATE; HEART VENTRICLE; MITOCHONDRION; MOUSE; MUSCLE CELL; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STIMULATION;

AEROBIOSIS; ANIMALS; CELLS, CULTURED; ENERGY METABOLISM; GENE DELETION; HEART; HEART DISEASES; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MICE; MICE, KNOCKOUT; MUSCLES; MYOCARDIAL ISCHEMIA; MYOCARDIUM; ORGAN CULTURE TECHNIQUES; ORGAN SPECIFICITY; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION;

MAMMALIA; MUS;

EID: 77953808195     PISSN: 09254439     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbadis.2010.04.008     Document Type: Article

References (34)

1. Bianchi A., Evans J.L., Iverson A.J., Nordlund A.C., Watts T.D., Witters L.A. Identification of an isozymic form of acetyl-CoA carboxylase. J. Biol. Chem. 1990, 265:1502-1509.
2. Carling D., Zammit V.A., Hardie D.G. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 1987, 223:217-222.
3. Cheng S.W., Fryer L.G., Carling D., Shepherd P.R. Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status. J. Biol. Chem. 2004, 279:15719-15722.
4. Cho Y.S., Lee J.I., Shin D., Kim H.T., Jung H.Y., Lee T.G., Kang L.W., Ahn Y.J., Cho H.S., Heo Y.S. Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK. Biochem. Biophys. Res. Commun. 2010, 391:187-192.
5. Dyck J.R., Barr A.J., Barr R.L., Kolattukudy P.E., Lopaschuk G.D. Characterization of cardiac malonyl-CoA decarboxylase and its putative role in regulating fatty acid oxidation. Am. J. Physiol. 1998, 275:H2122-H2129.
6. Folmes C.D., Wagg C.S., Shen M., Clanachan A.S., Tian R., Lopaschuk G.D. Suppression of 5'-AMP-activated protein kinase activity does not impair recovery of contractile function during reperfusion of ischemic hearts. Am. J. Physiol. Heart Circ. Physiol. 2009, 297:H313-H321.
7. Fujii N., Boppart M.D., Dufresne S.D., Crowley P.F., Jozsi A.C., Sakamoto K., Yu H., Aschenbach W.G., Kim S., Miyazaki H., Rui L., White M.F., Hirshman M.F., Goodyear L.J. Overexpression or ablation of JNK in skeletal muscle has no effect on glycogen synthase activity. Am. J. Physiol. Cell Physiol. 2004, 287(1):C200-C208.
8. Hedhli N., Pelat M., Depre C. Protein turnover in cardiac cell growth and survival. Cardiovasc. Res. 2005, 68:186-196.
9. Ikeda Y., Sato K., Pimentel D.R., Sam F., Shaw R.J., Dyck J.R., Walsh K. Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunction. J. Biol. Chem. 2009, 284:35839-35849.
10. Inoki K., Zhu T., Guan K.L. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003, 115:577-590.
11. Koh H.J., Arnolds D.E., Fujii N., Tran T.T., Rogers M.J., Jessen N., Li Y., Liew C.W., Ho R.C., Hirshman M.F., Kulkarni R.N., Kahn C.R., Goodyear L.J. Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. Mol. Cell. Biol. 2006, 26:8217-8227.
12. Kuang M., Febbraio M., Wagg C., Lopaschuk G.D., Dyck J.R. Fatty acid translocase/CD36 deficiency does not energetically or functionally compromise hearts before or after ischemia. Circulation 2004, 109:1550-1557.
13. Larsen T.S., Belke D.D., Sas R., Giles W.R., Severson D.L., Lopaschuk G.D., Tyberg J.V. The isolated working mouse heart: methodological considerations. Pflugers Arch. 1999, 437:979-985.
14. Liu B., Alaoui-Talibi Z., Clanachan A.S., Schulz R., Lopaschuk G.D. Uncoupling of contractile function from mitochondrial TCA cycle activity and MVO2 during reperfusion of ischemic hearts. Am. J. Physiol. 1996, 270:H72-H80.
15. Lizcano J.M., Goransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Makela T.P., Hardie D.G., Alessi D.R. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 2004, 23:833-843.
16. Merrill G.F., Kurth E.J., Hardie D.G., Winder W.W. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am. J. Physiol. 1997, 273:E1107-E1112.
17. Musi N., Fujii N., Hirshman M.F., Ekberg I., Froberg S., Ljungqvist O., Thorell A., Goodyear L.J. AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes 2001, 50:921-927.
18. Neubauer S. The failing heart-an engine out of fuel. N. Engl. J. Med. 2007, 356:1140-1151.
19. Noga A.A., Soltys C.L., Barr A.J., Kovacic S., Lopaschuk G.D., Dyck J.R. Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy. Am. J. Physiol. Heart Circ. Physiol. 2007, 292:H1460-H1469.
20. Rosenberger L.B., Jacobs L.W., Stanton H.C. Evaluation of cardiac anoxia and ischemia models in the rat using calcium antagonists. Life Sci. 1984, 34:1379-1387.
21. Russell R.R., Bergeron R., Shulman G.I., Young L.H. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am. J. Physiol. 1999, 277:H643-H649.
22. Russell R.R., Li J., Coven D.L., Pypaert M., Zechner C., Palmeri M., Giordano F.J., Mu J., Birnbaum M.J., Young L.H. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J. Clin. Invest. 2004, 114:495-503.
23. Saddik M., Gamble J., Witters L.A., Lopaschuk G.D. Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. J. Biol. Chem. 1993, 268:25836-25845.
24. Sakamoto K., McCarthy A., Smith D., Green K.A., Grahame H.D., Ashworth A., Alessi D.R. Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J. 2005, 24:1810-1820.
25. Sakamoto K., Zarrinpashneh E., Budas G.R., Pouleur A.C., Dutta A., Prescott A.R., Vanoverschelde J.L., Ashworth A., Jovanovic A., Alessi D.R., Bertrand L. Deficiency of LKB1 in heart prevents ischemia-mediated activation of AMPKalpha2 but not AMPKalpha1. Am. J. Physiol. Endocrinol. Metab. 2006, 290:E780-E788.
26. Semsarian C., Ahmad I., Giewat M., Georgakopoulos D., Schmitt J.P., McConnell B.K., Reiken S., Mende U., Marks A.R., Kass D.A., Seidman C.E., Seidman J.G. The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J. Clin. Invest. 2002, 109:1013-1020.
27. Shaw R.J., Lamia K.A., Vasquez D., Koo S.H., Bardeesy N., DePinho R.A., Montminy M., Cantley L.C. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005, 310:1642-1646.
28. Srere P.A. Citrate synthase. Methods Enzymol. 1969, 13:3-5.
29. Stanley W.C., Recchia F.A., Lopaschuk G.D. Myocardial substrate metabolism in the normal and failing heart. Physiol. Rev. 2005, 85:1093-1129.
30. Thomson D.M., Brown J.D., Fillmore N., Condon B.M., Kim H.J., Barrow J.R., Winder W.W. LKB1 and the regulation of malonyl-CoA and fatty acid oxidation in muscle. Am. J. Physiol. Endocrinol. Metab. 2007, 293:E1572-E1579.
31. Thomson D.M., Porter B.B., Tall J.H., Kim H.J., Barrow J.R., Winder W.W. Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice. Am. J. Physiol. Endocrinol. Metab. 2007, 292:E196-E202.
32. White H.D., Chew D.P. Acute myocardial infarction. Lancet 2008, 372:570-584.
33. Xie M., Zhang D., Dyck J.R., Li Y., Zhang H., Morishima M., Mann D.L., Taffet G.E., Baldini A., Khoury D.S., Schneider M.D. A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway. Proc. Natl. Acad. Sci. U S. A. 2006, 103:17378-17383.
34. Xing Y., Musi N., Fujii N., Zou L., Luptak I., Hirshman M.F., Goodyear L.J., Tian R. Glucose metabolism and energy homeostasis in mouse hearts overexpressing dominant negative alpha2 subunit of AMP-activated protein kinase. J. Biol. Chem. 2003, 278:28372-28377.