Pivotal role of mTORC2 and involvement of ribosomal protein S6 in cardioprotective signaling

Circulation Research

Volumn 114, Issue 8, 2014, Pages 1268-1280

  Yano, Toshiyuki ^a,d   Ferlito, Marcella ^a   Aponte, Angel ^b   Kuno, Atsushi ^d   Miura, Tetsuji ^d   Murphy, Elizabeth ^c   Steenbergen, Charles ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^d SAPPORO MEDICAL UNIVERSITY   (Japan)

Author keywords

insulin; ischemia reperfusion injury; ischemic preconditioning; mTORC2; myocardial ischemic reperfusion injury; rapamycin; sirolimus

Indexed keywords

INSULIN; ISCHEMIA-REPERFUSION INJURY; ISCHEMIC PRECONDITIONING; MTORC2; MYOCARDIAL ISCHEMIC REPERFUSION INJURY; RAPAMYCIN; SIROLIMUS;

ANIMALS; CELLS, CULTURED; DISEASE MODELS, ANIMAL; FEEDBACK, PHYSIOLOGICAL; ISCHEMIC PRECONDITIONING, MYOCARDIAL; MALE; MICE; MICE, INBRED C57BL; MULTIPROTEIN COMPLEXES; MYOCARDIAL ISCHEMIA; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; RIBOSOMAL PROTEIN S6; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84899110886     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.114.303562     Document Type: Article

References (45)

1. Miura T, Miki T. Limitation of myocardial infarct size in the clinical setting: current status and challenges in translating animal experiments into clinical therapy. Basic Res Cardiol. 2008;103:501-513.
2. Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev. 2008;88:581-609.
3. Tong H, Chen W, Steenbergen C, Murphy E. Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. Circ Res. 2000;87:309-315.
4. Gross ER, Hsu AK, Gross GJ. Opioid-induced cardioprotection occurs via glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts. Circ Res. 2004;94:960-966.
5. Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM. Postconditioning: a form of "modifed reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res. 2004;95:230-232.
6. Ban K, Cooper AJ, Samuel S, Bhatti A, Patel M, Izumo S, Penninger JM, Backx PH, Oudit GY, Tsushima RG. Phosphatidylinositol 3-kinase gamma is a critical mediator of myocardial ischemic and adenosine-mediated preconditioning. Circ Res. 2008;103:643-653.
7. Tong H, Rockman HA, Koch WJ, Steenbergen C, Murphy E. G protein-coupled receptor internalization signaling is required for cardio-protection in ischemic preconditioning. Circ Res. 2004;94:1133-1141.
8. Budas GR, Sukhodub A, Alessi DR, Jovanovic A. 3'Phosphoinositide- dependent kinase-1 is essential for ischemic preconditioning of the myocardium. FASEB J. 2006;20:2556-2558.
9. Miyamoto S, Purcell NH, Smith JM, Gao T, Whittaker R, Huang K, Castillo R, Glembotski CC, Sussman MA, Newton AC, Brown JH. PHLPP-1 negatively regulates Akt activity and survival in the heart. Circ Res. 2010;107:476-484.
10. Das S, Wong R, Rajapakse N, Murphy E, Steenbergen C. Glycogen syn-thase kinase 3 inhibition slows mitochondrial adenine nucleotide transport and regulates voltage-dependent anion channel phosphorylation. Circ Res. 2008;103:983-991.
11. Sun J, Morgan M, Shen RF, Steenbergen C, Murphy E. Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochon-drial energetics and calcium transport. Circ Res. 2007;101:1155-1163.
12. Nguyen TT, Stevens MV, Kohr M, Steenbergen C, Sack MN, Murphy E. Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore. J Biol Chem. 2011;286:40184-40192.
13. Miyamoto S, Murphy AN, Brown JH. Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ. 2008;15:521-529.
14. Smeele KM, Southworth R, Wu R, et al. Disruption of hexokinase II-mitochondrial binding blocks ischemic preconditioning and causes rapid cardiac necrosis. Circ Res. 2011;108:1165-1169.
15. Ferlito M, Fulton WB, Zauher MA, Marbán E, Steenbergen C, Lowenstein CJ. VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes. J Mol Cell Cardiol. 2010;49:791-800.
16. Sun J, Kohr MJ, Nguyen T, Aponte AM, Connelly PS, Esfahani SG, Gucek M, Daniels MP, Steenbergen C, Murphy E. Disruption of caveolae blocks ischemic preconditioning-mediated S-nitrosylation of mitochondrial proteins. Antioxid Redox Signal. 2012;16:45-56.
17. Yano T, Miki T, Tanno M, Kuno A, Itoh T, Takada A, Sato T, Kouzu H, Shimamoto K, Miura T. Hypertensive hypertrophied myocardium is vulnerable to infarction and refractory to erythropoietin-induced protection. Hypertension. 2011;57:110-115.
18. Huang J. An in vitro assay for the kinase activity of mTOR complex 2. Methods Mol Biol. 2012;821:75-86.
19. Xie X, Zhang D, Zhao B, Lu MK, You M, Condorelli G, Wang CY, Guan KL. IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation. Proc Natl Acad Sci USA. 2011;108:6474-6479.
20. Zhang H, Zha X, Tan Y, Hornbeck PV, Mastrangelo AJ, Alessi DR, Polakiewicz RD, Comb MJ. Phosphoprotein analysis using antibodies broadly reactive against phosphorylated motifs. J Biol Chem. 2002;277:39379-39387.
21. Kane S, Sano H, Liu SC, Asara JM, Lane WS, Garner CC, Lienhard GE. A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain. J Biol Chem. 2002;277:22115-22118.
22. Kobayashi H, Miura T, Ishida H, Miki T, Tanno M, Yano T, Sato T, Hotta H, Shimamoto K. Limitation of infarct size by erythropoietin is associated with translocation of Akt to the mitochondria after reperfusion. Clin Exp Pharmacol Physiol. 2008;35:812-819.
23. Zinzalla V, Stracka D, Oppliger W, Hall MN. Activation of mTORC2 by association with the ribosome. Cell. 2011;144:757-768.
24. Panic L, Tamarut S, Sticker-Jantscheff M, Barkic M, Solter D, Uzelac M, Grabusic K, Volarevic S. Ribosomal protein S6 gene haploinsuffciency is associated with activation of a p53-dependent checkpoint during gastrula-tion. Mol Cell Biol. 2006;26:8880-8891.
25. Carew JS, Kelly KR, Nawrocki ST. Mechanisms of mTOR inhibitor resistance in cancer therapy. Target Oncol. 2011;6:17-27.
26. Liao Y, Hung MC. Physiological regulation of Akt activity and stability. Am J Transl Res. 2010;2:19-42.
27. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307:1098-1101.
28. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, Shokat KM. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol. 2009;7:e38.
29. Völkers M, Konstandin MH, Doroudgar S, Toko H, Quijada P, Din S, Joyo A, Ornelas L, Samse K, Thuerauf DJ, Gude N, Glembotski CC, Sussman MA. Mechanistic target of rapamycin complex 2 protects the heart from ischemic damage. Circulation. 2013;128:2132-2144.
30. Cameron AJ, Linch MD, Saurin AT, Escribano C, Parker PJ. mTORC2 targets AGC kinases through Sin1-dependent recruitment. Biochem J. 2011;439:287-297.
31. Warner JR, McIntosh KB. How common are extraribosomal functions of ribosomal proteins? Mol Cell. 2009;34:3-11.
32. Wong R, Aponte AM, Steenbergen C, Murphy E. Cardioprotection leads to novel changes in the mitochondrial proteome. Am J Physiol Heart Circ Physiol. 2010;298:H75-H91.
33. Nguyen T, Wong R, Wang G, Gucek M, Steenbergen C, Murphy E. Acute inhibition of GSK causes mitochondrial remodeling. Am J Physiol Heart Circ Physiol. 2012;302:H2439-H2445.
34. Thornton J, Striplin S, Liu GS, Swafford A, Stanley AW, Van Winkle DM, Downey JM. Inhibition of protein synthesis does not block myocardial protection afforded by preconditioning. Am J Physiol. 1990;259:H1822-H1825.
35. Oh WJ, Jacinto E. mTOR complex 2 signaling and functions. Cell Cycle. 2011;10:2305-2316.
36. Bracho-Valdés I, Moreno-Alvarez P, Valencia-Martínez I, Robles-Molina E, Chávez-Vargas L, Vázquez-Prado J. mTORC1-and mTORC2-interacting proteins keep their multifunctional partners focused. IUBMB Life. 2011;63:896-914.
37. Ruvinsky I, Katz M, Dreazen A, Gielchinsky Y, Saada A, Freedman N, Mishani E, Zimmerman G, Kasir J, Meyuhas O. Mice defcient in ribo-somal protein S6 phosphorylation suffer from muscle weakness that refects a growth defect and energy defcit. PLoS One. 2009;4:e5618.
38. Lee SB, Kwon IS, Park J, Lee KH, Ahn Y, Lee C, Kim J, Choi SY, Cho SW, Ahn JY. Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. J Biol Chem. 2010;285:29457-29468.
39. Kohr MJ, Aponte AM, Sun J, Wang G, Murphy E, Gucek M, Steenbergen C. Characterization of potential S-nitrosylation sites in the myocardium. Am J Physiol Heart Circ Physiol. 2011;300:H1327-H1335.
40. Jonassen AK, Sack MN, Mjøs OD, Yellon DM. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ Res. 2001;89:1191-1198.
41. Vigneron F, Dos Santos P, Lemoine S, Bonnet M, Tariosse L, Couffnhal T, Duplaà C, Jaspard-Vinassa B. GSK-3β at the crossroads in the signalling of heart preconditioning: implication of mTOR and Wnt pathways. Cardiovasc Res. 2011;90:49-56.
42. Park SS, Zhao H, Jang Y, Mueller RA, Xu Z. N6-(3-iodobenzyl)-adenosine- 5'-N-methylcarboxamide confers cardiopro-tection at reperfusion by inhibiting mitochondrial permeability transition pore opening via glycogen synthase kinase 3 beta. J Pharmacol Exp Ther. 2006;318:124-131.
43. Khan S, Salloum F, Das A, Xi L, Vetrovec GW, Kukreja RC. Rapamycin confers preconditioning-like protection against ischemia-reperfusion injury in isolated mouse heart and cardiomyocytes. J Mol Cell Cardiol. 2006;41:256-264.
44. El-Ani D, Stav H, Guetta V, Arad M, Shainberg A. Rapamycin (sirolimus) protects against hypoxic damage in primary heart cultures via Na+/Ca2+ exchanger activation. Life Sci. 2011;89:7-14.
45. Shende P, Plaisance I, Morandi C, Pellieux C, Berthonneche C, Zorzato F, Krishnan J, Lerch R, Hall MN, Rüegg MA, Pedrazzini T, Brink M. Cardiac raptor ablation impairs adaptive hypertrophy, alters metabolic gene expression, and causes heart failure in mice. Circulation. 2011;123:1073-1082.