Journal of Molecular Histology

, Volume 44, Issue 5, pp 565–573

Expression and redistribution of β-catenin in the cardiac myocytes of left ventricle of spontaneously hypertensive rat

  • Qiaoli Zheng
  • Ping Chen
  • Zeqing Xu
  • Faqian Li
  • Xian Ping Yi
Original Paper


Beta-catenin is not only an adhering junction protein, but also the central player of the canonical Wnt signalling pathway. In order to investigate the roles of β-catenin in the mechanism of myocardial hypertrophy, we determined the expression and distribution of β-catenin in the cardiomyocytes of spontaneously hypertensive heart failure (SHHF) rats and age-matched Wistar-Kyoto (WKY) rats. We identified the reducing of β-catenin expression in the membrane protein fraction but increasing in the nuclear protein in the 6 and 12 month-old SHHF rats as compared with the age-matched WKY rats by Western blotting. Immunolabeling of β-catenin colocalized with cadherin at the intercalated disc sites and showed nuclear accumulation in myocytes of SHHF rats. We also revealed that the association between glycogen synthase kinase-3β and β-catenin had weakened in the 6 month-old SHHF rats as compared with the age-matched WKY rats by immunoprecipitation. These findings suggested that nuclear translocation of β-catenin might play important roles in regulating signal transduction in the decompensated hypertrophy stage.


Cardiac hypertrophy Beta-catenin Cadherin Glycogen synthase kinase-3β (GSK3β) Signal transduction 


  1. Alain H, Adrien C, Evelyne P, Roman S, Irina A, Hoerstrup SP, Taketo MM, Pedrazzini T, Perriard JC, Ehler E (2010) Stabilised beta-catenin in postnatal ventricular myocardium leads to dilated cardiomyopathy and premature death. J Basic Res Cardiol 105:597–608CrossRefGoogle Scholar
  2. Ana LG, Maria D, Vivanco M, Robert MK (2000) α-catenin inhibits β-catenin signaling by preventing formation of a β-catenin.T-cell factor DNA complex. J Biol Chem 275:21883–21888CrossRefGoogle Scholar
  3. Behrens J, Jerchow BA, Würtele M, Grimm J, Asbrand C, Wirtz R, Kühl M, Wedlich D, Birchmeier W (1998) Functional interaction of an axin homolog, conduction, with beta-catenin, APC, and GSK3. Science 280:596–599PubMedCrossRefGoogle Scholar
  4. Blough E, Dineen B, Esser K (1996) Extraction of nuclear proteins from striated muscle tissue. J Biotech 26(202–204):206Google Scholar
  5. Brancaccio M, Fratta L, Notte A, Hirsch E, Poulet R, Guazzone S, De Acetis M, Vecchione C, Marino G, Altruda F, Silengo L, Tarone G, Lembo G (2003) Melusin, a muscle-specific integrin b1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload. Nat Med 9:68–75PubMedCrossRefGoogle Scholar
  6. Cox RT, Kirkpatrick C, Peifer M (1996) Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during drosophila embryogenesis. J Cell Biol 134:133–148PubMedCrossRefGoogle Scholar
  7. de Barros EP, Garcia-Pinto AB, Machado PY, dos Santos Pereira MJ, de Carvalho JJ (2011) Rosuvastatin beneficially alters the glomerular structure of kidneys from spontaneously hypertensive rats (SHRs). J Mol Histol 42(4):323–331PubMedCrossRefGoogle Scholar
  8. Fagotto F, Funayama N, Gluck U, Gumbiner B (1996) Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in xenopus. J Cell Biol 132:1105–1114PubMedCrossRefGoogle Scholar
  9. Gottardi CJ, Gumbiner BM (2004) Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes. J Cell Biol 167:339–349PubMedCrossRefGoogle Scholar
  10. Haq S, Choukroun G, Lim H, Tymitz KM, del Monte F, Gwathmey J, Grazette L, Michael A, Hajjar R, Force T, Molkentin JD (2001) Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure. Circulation 103:670–677PubMedCrossRefGoogle Scholar
  11. Heasman J, Crawford A, Goldstone K, GarnerHamrick P, Gumbiner B, McCrea P, Kintner C, Noro C, Wylie C (1994) Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. J Cell 79:791–803CrossRefGoogle Scholar
  12. Kuppuswamy D, Kerr C, Narishige T, Kasi VS, Menick DR, Cooper G IV (1997) Association of tyrosine-phosphorylated c-Src with the cytoskeleton of hypertrophying myocardium. J Biol Chem 272:4500–4508PubMedCrossRefGoogle Scholar
  13. Laura M, Roberto B, Pamela S, Ilaria S, Paola F, Loredana A, Anna C, Camilla P, Marilena M, Roberta F, Felicia C, Cristina F, Luciana C, Andrea M, Di Paolo N (2003) β-catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts. J Cardiovasc Res 60:376–387CrossRefGoogle Scholar
  14. Li Z, Yi XP, Zhong L, Li F, Zhou W, Cao W, Zhen Y, Wang X, Wang Y (2007) Expression of focal adhesion kinase in cardiac myocytes of hypertrophic ventricle. Chin J Pathol 36:677–680Google Scholar
  15. Li L, Wang X, Xie Y, Li Z, Cao W, Yi XP (2011) Membrane translocation of Src kinase in cardiac myocytes of hypertrophic left ventricle of hypertensive rats. Chin Heart J 23:295–299Google Scholar
  16. Manisastry SM, Han M, Linask KK (2006) Early temporal-specific responses and differential sensitivity to lithium and Wnt-3A exposure during heart development. J Dev Dyn 235:2160–2174CrossRefGoogle Scholar
  17. Mara B, Hirsch Emilio, Notte Antonella, Selvetella Giulio, Lembo Giuseppe, Tarone Guido (2006) Integrin signalling: the tug-of-war in heart hypertrophy. J Cardiovasc Res 70:422–433CrossRefGoogle Scholar
  18. Marisa MF, Jérôme T, Marie-Ange D, Walter B, Joerg H, Jean PL, Amparo C, Marina AG (2007) Beta-catenin regulates P-cadherin expression in mammary basal epithelial cells. J FEBS Lett 581:831–836CrossRefGoogle Scholar
  19. Onodera T, Tamura T, Said S, McCune SA, Gerdes AM (1998) Maladaptive remodeling of cardiac myocyte shape begins long before failure in hypertension. Hypertension 32:753–757PubMedCrossRefGoogle Scholar
  20. Oscar HC (2007) Cardiac hypertrophy and the Wnt/frizzle pathway. Hypertension 49:427–428CrossRefGoogle Scholar
  21. Rebecca LD, Cara JG (2007) Phospho-regulation of ß-catenin adhesion and signaling functions. J Physiol 22:303–309CrossRefGoogle Scholar
  22. Shevtsov SP, Haq S, Force T (2006) Activation of beta-catenin signaling pathways by classical G-protein-coupled receptors: mechanisms and consequences in cycling and non-cycling cells. Cell Cycle 5:2295–2300PubMedCrossRefGoogle Scholar
  23. Syed H, Michael A, Andreucci M, Bhattacharya K, Dotto P, Walters B, Woodgett J, Kilter H, Force T (2003) Stabilization of betacatenin by a Wnt-independent mechanism regulates cardiomyocyte growth. J Proc Natl Acad Sci USA 100:4610–4615CrossRefGoogle Scholar
  24. Van Johan HES, Barker N, Clevers H (2003) You Wnt some, you lose some: oncogenes in the Wnt signaling pathway. Curr Opin Genet Dev 13:28–33CrossRefGoogle Scholar
  25. Xin C, Shevtsov SP, Hsich E, Cui L, Haq S, Kerkela R, Molkentin JD, Liao R, Salomon RN, Patten R, Force T (2006) The ß-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy. J Mol Cell Biol 26:4462–4473CrossRefGoogle Scholar
  26. Yi XP, Gerdes AM, Li F (2002) Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure–prone rats. Hypertension 39:1058–1063PubMedCrossRefGoogle Scholar
  27. Yi XP, Zhou J, Huber L, Qu J, Wang X, Martin Gerdes A, Li F (2006) Nuclear compartmentalization of FAK and FRNK in cardiac myocytes. Am J Physiol Heart Circ Physiol 290:H2509–H2515PubMedCrossRefGoogle Scholar
  28. Zhang CG, Jia ZQ, Li BH, Zhang H, Liu YN, Chen P, Ma KT, Zhou CY (2009) Beta-catenin/TCF/LEF1 can directly regulate phenylephrine-induced cell hypertrophy and Anf transcription in cardiomyocytes. J Biochem Biophys Res Commun 390:258–262CrossRefGoogle Scholar
  29. Zhou H, Yang HX, Yuan Y, Deng W, Zhang JY, Bian ZY, Zong J, Dai J, Tang QZ (2013) Paeoniflorin attenuates pressure overload-induced cardiac remodeling via inhibition of TGFβ/Smads and NF-κB pathways. J Mol Histol. 2013 Feb 17. [Epub ahead of print] PubMed PMID: 23417833Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Qiaoli Zheng
    • 1
  • Ping Chen
    • 2
  • Zeqing Xu
    • 1
  • Faqian Li
    • 3
  • Xian Ping Yi
    • 1
  1. 1.Department of PathologySun Yat-sen University the Fifth Affiliated HospitalZhuhaiPeople’s Republic of China
  2. 2.Department of PathologyJiangmen Central HospitalJiangmenPeople’s Republic of China
  3. 3.Department of Pathology and Laboratory MedicineUniversity of Rochester Medical CenterRochesterUSA

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