The alteration of protein prenylation induces cardiomyocyte hypertrophy through Rheb-mTORC1 signalling and leads to chronic heart failure

Journal of Pathology

Volumn 235, Issue 5, 2015, Pages 672-685

  Xu, Na ^a   Guan, Shan ^c   Chen, Zhong ^a   Yu, Yang ^d   Xie, Jun ^b   Pan, Fei Yan ^c   Zhao, Ning Wei ^f   Liu, Li ^e   Yang, Zhong Zhou ^a   Gao, Xiang ^a   Xu, Biao ^b   Li, Chao Jun ^a  

^a NANJING UNIVERSITY   (China)

^b MEDICAL SCHOOL OF NANJING UNIVERSITY   (China)

^c NANJING NORMAL UNIVERSITY   (China)

^d INSTITUTE OF ZOOLOGY   (China)

^e NANJING MEDICAL UNIVERSITY   (China)

^f Shimadzu (China) Co Ltd   (China)

Author keywords

cardiac hypertrophy; GGPPS; protein prenylation; Rheb

Indexed keywords

FARNESYL DIPHOSPHATE; FARNESYL TRANS TRANSFERASE; GERANYLGERANYL PYROPHOSPHATE; GUANINE NUCLEOTIDE BINDING PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; RHEB PROTEIN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MONOMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; MULTIPROTEIN COMPLEX; NEUROPEPTIDE; PROTEIN KINASE INHIBITOR; RAPAMYCIN; RHEB PROTEIN, RAT; TARGET OF RAPAMYCIN KINASE;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA CONSTRICTION; ARTICLE; CELL MEMBRANE; CONTROLLED STUDY; DEATH; DOWN REGULATION; FARNESYLATION; HEART DEVELOPMENT; HEART FAILURE; HEART FUNCTION; HEART MUSCLE CELL; HEART SIZE; HEART VENTRICLE HYPERTROPHY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROPHOBICITY; IN VIVO STUDY; MOUSE; MUSCLE HYPERTROPHY; NEWBORN; NONHUMAN; POSTNATAL GROWTH; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN MODIFICATION; PROTEIN PRENYLATION; RAT; SIGNAL TRANSDUCTION; TANDEM MASS SPECTROMETRY; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CARDIOMEGALY; CELL LINE; DEFICIENCY; DISEASE COURSE; DISEASE MODEL; DRUG EFFECTS; ENZYMOLOGY; FEMALE; GENETIC TRANSFECTION; GENETICS; HEART LEFT VENTRICLE FUNCTION; KNOCKOUT MOUSE; MALE; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; RNA INTERFERENCE; SPRAGUE DAWLEY RAT; TIME;

ANIMALS; CARDIOMEGALY; CELL LINE; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; FARNESYLTRANSTRANSFERASE; FEMALE; HEART FAILURE; MALE; MICE, INBRED C57BL; MICE, KNOCKOUT; MONOMERIC GTP-BINDING PROTEINS; MULTIPROTEIN COMPLEXES; MYOCYTES, CARDIAC; NEUROPEPTIDES; PROTEIN KINASE INHIBITORS; PROTEIN PRENYLATION; RATS; RATS, SPRAGUE-DAWLEY; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SIROLIMUS; TIME FACTORS; TOR SERINE-THREONINE KINASES; TRANSFECTION; VENTRICULAR FUNCTION, LEFT;

EID: 84924544203     PISSN: 00223417     EISSN: 10969896     Source Type: Journal    
DOI: 10.1002/path.4480     Document Type: Article

References (52)

1. Heineke J, Molkentin J,. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 2006; 7: 589-600.
2. Sah VP, Minamisawa S, Tam SP, et al., Cardiac-specific overexpression of Rhoa results in sinus and atrioventricular nodal dysfunction and contractile failure. J Clin Invest 1999; 103: 1627-1634.
3. Sussman MA, Welch S, Walker A, et al., Altered focal adhesion regulation correlates with cardiomyopathy in mice expressing constitutively active rac1. J Clin Invest 2000; 105: 875-896.
4. Hunter J, Tanaka N, Rockman H, et al., Ventricular expression of a MLC-2v-ras fusion gene induces cardiac hypertrophy and selective diastolic dysfunction in transgenic mice. J Biol Chem 1995; 270: 23173.
5. Wang Y, Huang BP, Luciani DS, et al., Rheb activates protein synthesis and growth in adult rat ventricular cardiomyocytes. J Mol Cell Cardiol 2008; 45: 812-820.
6. Casey PJ,. Protein lipidation in cell signaling. Science 1995; 268: 221-225.
7. Perez-Sala D., Protein isoprenylation in biology and disease: general overview and perspectives from studies with genetically engineered animals. Front Biosci 2007; 12: 4456-4472.
8. Konstantinopoulos PA, Karamouzis MV, Papavassiliou AG,. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nat Rev Drug Discov 2007; 6: 541-555.
9. Walker K, Olson MF,. Targeting Ras and Rho GTPases as opportunities for cancer therapeutics. Curr Opin Genet Dev 2005; 15: 62-68.
10. Yi P, Han Z, Li X, et al., The mevalonate pathway controls heart formation in Drosophila by isoprenylation of γ1. Science 2006; 313: 1301.
11. Li L, Chen G, Yang Y, et al., Chronic inhibition of farnesyl pyrophosphate synthase attenuates cardiac hypertrophy and fibrosis in spontaneously hypertensive rats. Biochem Pharmacol 2010; 79: 399-406.
12. Yang J, Mou Y, Wu T, et al., Cardiac-specific overexpression of farnesyl pyrophosphate synthase induces cardiac hypertrophy and dysfunction in mice. Cardiovasc Res 2013; 97: 490-499.
13. Liao J., Statin therapy for cardiac hypertrophy and heart failure. J Invest Med 2004; 52: 248.
14. Takemoto M, Node K, Nakagami H, et al., Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 2001; 108: 1429-1494.
15. Tomaszewski M, Stêpieñ KM, Tomaszewska J, et al., Statin-induced myopathies. Pharmacol Rep 2011; 63: 859-866.
16. Mammen A, Amato A,. Statin myopathy: a review of recent progress. Curr Opin Rheumatol 2010; 22: 644.
17. Wang X-X, Ying P, Diao F, et al., Altered protein prenylation in Sertoli cells is associated with adult infertility resulting from childhood mumps infection. J Exp Med 2013; 210: 1559-1574.
18. Scott Reid T, Terry KL, Casey PJ, et al., Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J Mol Res 2004; 343: 417-433.
19. Ashby MN,. CaaX converting enzymes. Curr Opin Lipidol 1998; 9: 99-102.
20. Ericsson JMG, Carter KC, Shell BK, et al., Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression. J Lipid Res 1998; 39: 1731-1739.
21. Zoltan Arany MN, Chin S, Ma Y, et al., Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-γ coactivator 1α. Proc Natl Acad Sci USA 2006; 103: 10086-10091.
22. Nikolskaya A, Sharma V,. Cell culture models and methods. In Cardiac Electrophysiol Methods Models, Sigg DC, Laizzo PA, Xiao YF, et al. (eds). Springer: New York, NY, 2010, 213-235.
23. Shen N, Yu X, Pan FY, et al., An early response transcription factor, Egr-1, enhances insulin resistance in type 2 diabetes with chronic hyperinsulinism. J Biol Chem 2011; 286: 14508-14515.
24. Blonder J, Chan KC, Issaq HJ, et al., Identification of membrane proteins from mammalian cell/tissue using methanol-facilitated solubilization and tryptic digestion coupled with 2D LC-MS/MS. Nat Protoc 2007; 1: 2784-2790.
25. Sambrook J, Russell DW,. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 2001.
26. Tong H, Wiemer AJ, Neighbors JD, et al., Quantitative determination of farnesyl and geranylgeranyl diphosphate levels in mammalian tissue. Anal Biochem 2008; 378: 138-143.
27. Tamai T, Yamaguchi O, Hikoso S, et al., Rheb (ras homologue enriched in brain)-dependent mammalian target of rapamycin complex 1 (mTORC1) activation becomes indispensable for cardiac hypertrophic growth after early postnatal period. J Biol Chem 2013; 288: 10176-10187.
28. Goodman C, Miu M, Frey J, et al., A PI3K/PKB-independent activation of mTOR signaling is sufficient to induce skeletal muscle hypertrophy. Mol Biol Cell 2010; 21: 3258-3268.
29. Castro AF, Rebhun JF, Clark GJ, et al., Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem 2003; 278: 32493.
30. Zoncu R, Efeyan A, Sabatini DM,. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2010; 12: 21-35.
31. Wu X, Cao Y, Nie J, et al., Genetic and pharmacological inhibition of Rheb1-mTORC1 signaling exerts cardioprotection against adverse cardiac remodeling in mice. Am J Pathol 2013; 182: 2005-2014.
32. van Berlo JH, Maillet M, Molkentin JD,. Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest 2013; 123: 37-45.
33. Finckenberg P, Mervaala E,. Novel regulators and drug targets of cardiac hypertrophy. J Hypertens 2010; 28: S33.
34. Bulhak AJR, Hedin U, Sjöquist PO, et al., Cardioprotective effect of rosuvastatin in vivo is dependent on inhibition of geranylgeranyl pyrophosphate and altered RhoA membrane translocation. Am J Physiol Heart Circ Physiol 2007; 292: H3158-3163.
35. Somekawa S, Fukuhara S, Nakaoka Y, et al., Enhanced functional gap junction neoformation by protein kinase A-dependent and Epac-dependent signals downstream of cAMP in cardiac myocytes. Circ Res 2005; 97: 655-662.
36. Jeyaraj SC, Unger NT, Chotani MA,. Rap1 GTPases: an emerging role in the cardiovasculature. Life Sci 2011; 88: 645-652.
37. Dong W, Yang Z, Yang F, et al., Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish. PLoS One 2012; 7: e50960.
38. Xiang SY, Vanhoutte D, Del Re DP, et al., RhoA protects the mouse heart against ischemia/reperfusion injury. J Clin Invest 2011; 121: 3269-3276.
39. Lauriol J, Keith K, Jaffré F, et al,. RhoA signaling in cardiomyocytes protects against stress-induced heart failure but facilitates cardiac fibrosis. Sci Signal 2014; 7: ra100-ra100.
40. Hutagalung AH, Novick PJ,. Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev 2011; 91: 119-149.
41. Lee CH, Inoki K, Guan KL,. mTOR pathway as a target in tissue hypertrophy. Annu Rev Pharmacol Toxicol 2007; 47: 443-467.
42. Shioi T, McMullen JR, Tarnavski O, et al., Rapamycin attenuates load-induced cardiac hypertrophy in mice. Circulation 2003; 107: 1664-1670.
43. Ikeda Y, Sato K, Pimentel DR, et al., Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunction. J Biol Chem 2009; 284: 35839-35849.
44. Malhowski AJ, Hira H, Bashiruddin S, et al., Smooth muscle protein-22-mediated deletion of Tsc1 results in cardiac hypertrophy that is mTORC1-mediated and reversed by rapamycin. Hum Mol Genet 2011; 20: 1290-1305.
45. Zhang D, Contu R, Latronico M, et al., MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. J Clin Invest 2010; 120: 2805-2816.
46. Shen W-H, Chen Z, Shi S, et al., Cardiac restricted overexpression of kinase-dead mammalian target of rapamycin (mTOR) mutant impairs the mTOR-mediated signaling and cardiac function. J Biol Chem 2008; 283: 13842-13849.
47. Song X, Kusakari Y, Xiao CY, et al., mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy. Am J Physiol Cell Physiol 2010; 299: C1256-1266.
48. Mendell JT, Olson EN,. MicroRNAs in stress signaling and human disease. Cell 2012; 148: 1172-1187.
49. Divakaran V, Mann DL,. The emerging role of microRNAs in cardiac remodeling and heart failure. Circ Res 2008; 103: 1072-1083.
50. van Rooij E, Sutherland LB, Liu N, et al., A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci USA 2006; 103: 18255-18260.
51. Martins PADC, De Windt LJ,. MicroRNAs in control of cardiac hypertrophy. Cardiovasc Res 2012; 93: 563-572.
52. Sayed D, Hong C, Chen IY, et al., MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 2007; 100: 416-424.