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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2013; 59(6): 124-131


The expression of Akt kinase in the heart ventricles under hypoxic preconditioning and myocardial remodeling

Portnichenko AG1, Lapikova-Briginskaia TIu2, Vasilenko MI2, Portnichenko GV2, Maslov LN3, Moĭbenko AA2

  1. International Centre for Astronomical, Medical and Ecological Research, NAS of Ukraine, Kyiv, Ukraine;
  2. Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
  3. FGBO SRI of Cardiology, Siberian Branch of RAMS, Tomsk, Russia
DOI: https://doi.org/10.15407/fz59.06.124

Abstract

Activation of Akt-dependent mechanisms may play a significant role in the cellular response under hypoxic preconditioning and myocardial remodeling. The impact of hypoxic preconditioning, and remodeling on the expression of Akt kinase in the heart ventricles was investigated. Wistar male rats, the residents of plains or middle altitude (2100 m above sea level), were exposed to hypoxic preconditioning by "lifting" in the barochamber at the "height" of 5,600 m in 3 h. In the right and left ventricles of the heart, Akt protein expression was determined by Western blotting. It was shown, that hypoxic preconditioning causes the induction of Akt kinase in the ventricles during the period of delayed cardioprotection (1-3 days after preconditioning). Myocardial remodeling induced by chronic hypoxia in middle altitude was associated with elevated Akt expression in the myocardium, more pronounced in the left ventricle. Progression of hypoxic myocardial remodeling found in part of the animals was accompanied by a reduction of the cell hypoxic reactivity, including Akt induction in response to preconditioning. Thus, Akt kinase is involved in the mechanisms of hypoxia induced late preconditioning and myocardial remodeling in chronic hypoxia. Inhibitory regulatory mechanism was found to limit the induction of Akt in myocardium after remodeling.

Keywords: hypoxic myocardial preconditioning, hypoxicmyocardial remodeling, Akt kinase expression

References

  1. Ananthakrishnan R., Moe G.W., Goldenthal M.J., Marin- Garcia J. Akt signaling pathway in pacing-induced heart failure . Mol. Cell. Biochem. 2005. 268. P. 103-110. CrossRef PubMed
  2.  
  3. Armstrong S.C. Protein kinase activation and myocardial ischemia. reperfusion injury . Cardiovasc. Res. 2004. 61. P. 427-436. CrossRef PubMed
  4.  
  5. Bae S., Zhang L. Gender differences in cardioprotection against ischemia. reperfusion injury in adult rat hearts: focus on Akt and protein kinase C signaling . J. Pharmacol. Exp. Ther. 2005. 315. P. 1125-1135. CrossRef PubMed
  6.  
  7. Bergmann O., Bhardwaj R.D., Bernard S., Zdunek S., Barnabe-Heider F., Walsh S., Zupicich J., Alkass K., Buchholz B.A., Druid H., Jovinge S., Frisen J. Evidence for cardiomyocytes renewal in humans . Science. 2009. 324. P. 98-102. CrossRef PubMed PubMedCentral
  8.  
  9. Bicknell K.A., Coxon C.H., Brooks G. Can the cardiomyocyte cell cycle be reprogrammed? . J. Mol. Cell. Cardiol. 2007. 42. P. 706-721. CrossRef PubMed
  10.  
  11. Ceci M., Gallo P., Santonastasi M., Grimaldi S., Latronico M.V., Pitisci A., Missol-Kolka E., Scimia M.C., Catalucci D., Hilfiker-Kleiner D., Condorelli G. Cardiac-specific overexpression of E40K active Akt prevents pressure overload-induced heart failure in mice by increasing angiogenesis and reducing apoptosis . Cell. Death. Differ. 2007. 14. P. 1060-1062. CrossRef  
  12. Cittadini A., Monti M.G., Iaccarino G., Di Rella F., Tsichlis P.N., Di Gianni A., Stromer H., Sorriento D., Peschle C., Trimarco B., Sacca L., Condorelli G. Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling . Gene Ther. 2006. 13. P. 8-19. CrossRef PubMed PubMedCentral
  13.  
  14. De Jonge N., Goumans M.J., Lips D., Hassink R., Vlug E.J., van der Meel R., Emmerson C.D., Nijman J., de Windt L., Doevendans P.A. Controlling cardiomyocyte survival . Novartis Found Symp. 2006. 274. P. 41-51. CrossRef  
  15. Dimmeler S., Zeiher A.M. Exercise and cardiovascular health: get active to "AKTivate" your endothelial nitric oxide synthase . Circulation. 2003. 107. P. 3118-3120. CrossRef PubMed
  16.  
  17. Evans-Anderson H.J., Alfieri C.M., Yutzey K.E. Regulation of cardiomyocyte proliferation and myocardial growth during development by FOXO transcription factors . Circ. Res. 2008. 102. P. 686-694. CrossRef PubMed
  18.  
  19. Gosselin H., Beliveau L. Burelle Y., Clement R., Lajoie C., El-Helou V., Calderone A. Disparate regulation of signaling proteins after exercise and myocardial infarction . Med. Sci. Sports Exercise. 38. P. 455-462. CrossRef PubMed
  20.  
  21. Kerkela R., Kockeritz L., Macaulay K., Zhou J., Doble B.W., Beahm C., Greytak S., Woulfe K., Trivedi C.M., Woodgett J.R., Epstein J.A., Force T., Huggins G.S. Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation . J. Clin. Invest. 118. P. 3609-3618. CrossRef PubMed PubMedCentral
  22.  
  23. Khan M., Mohsin S., Avitabile D., Siddiqi S., Nguyen J., Wallach K., Quijada P., McGregor M., Gude N., Alvarez R., Tilley D.G., Koch W.J., Sussman M.A. ?-Adrenergic regulation of cardiac progenitor cell death versus survival and proliferation . Circ. Res. 2013. 112. P. 476-486. CrossRef PubMed PubMedCentral
  24.  
  25. Ledvenyiova V., Pancza D., Matejikova J., Ferko M., Bernatova I., Ravingerova T. Impact of age and sex on response to ischemic preconditioning in the rat heart: differential role of the PI3K-AKT pathway . Can. J. Physiol. Pharmacol. 2013. 91. P. 640-647. CrossRef PubMed
  26.  
  27. Oudit G.Y., Penninger J.M. Cardiac regulation by phosphoinositide 3-kinases and PTEN . Cardiovasc. Res. 2009. 82. P. 250-260. CrossRef PubMed
  28.  
  29. Ravingerova T., Matejikova J., Neckar J., Andelova E., Kolar F. Differential role of PI3K. Akt pathway in the infarct size limitation and antiarrhythmic protection in the rat heart . Mol. Cell. Biochem. 2007. 297. P. 111-120. CrossRef PubMed
  30.  
  31. Rota M., Boni A., Urbanek K., Padin-Iruegas M.E., Kajstura T.J., Fiore G., Kubo H., Sonnenblick E.H., Musso E., Houser S.R., Leri A., Sussman M.A., Anversa P. Nuclear targeting of Akt enhances ventricular function and myocyte contractility . Circ. Res. 2005. 97. P. 1332-1341. CrossRef PubMed
  32.  
  33. Rubio M., Avitabile D., Fischer K., Emmanuel G., Gude N., Miyamoto S., Mishra S., Schaefer E.M., Brown J.H., Sussman M.A. Cardioprotective stimuli mediate phosphoinositide 3-kinase and phosphoinositide dependent kinase 1 nuclear accumulation in cardiomyocytes . J. Mol. Cell. Cardiol. 2009. 47. P. 96-103. CrossRef PubMed PubMedCentral
  34.  
  35. Shiojima I., Walsh K. Regulation of cardiac growth and coronary angiogenesis by the Akt. PKB signaling pathway . Genes Dev. 2006. 20. P. 3347-3365. CrossRef PubMed
  36.  
  37. Sussman M.A., Volkers M., Fischer K., Bailey B., Cottage C.T., Din S., Gude N., Avitabile D., Alvarez R., Sundararaman B., Quijada P., Mason M., Konstandin M.H., Malhowski A., Cheng Z., Khan M., McGregor M. Myocardial AKT: the omnipresent nexus . Physiol. Rev. 2011. 91. P. 1023-1070. CrossRef PubMed PubMedCentral
  38.  
  39. Taniyama Y., Ito M., Sato K., Kuester C., Veit K., Tremp G., Liao R., Colucci W.S., Ivashchenko Y., Walsh K., Shiojima I. Akt3 overexpression in the heart results in progression from adaptive to maladaptive hypertrophy . J. Mol. Cell. Cardiol. 2005. 38. P. 375-385. CrossRef PubMed
  40.  
  41. Tateishi K., Ashihara E., Honsho S., Takehara N., Nomura T., Takahashi T., Ueyama T., Yamagishi M., Yaku H., Matsubara H., Oh H. Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt. GSK-3beta signaling . Biochem. Biophys. Res. Commun. 2007. 352. P. 635-641. CrossRef PubMed
  42.  
  43. Tsujita Y., Muraski J., Shiraishi I., Kato T., Kajstura J., Anversa P., Sussman M.A. Nuclear targeting of Akt antagonizes aspects of cardiomyocyte hypertrophy . Proc. Natl. Acad. Sci. USA. 2006. 103. P. 11946-11951. CrossRef PubMed PubMedCentral
  44.  
  45. Urbanek K., Rota M., Cascapera S., Bearzi C., Nascimbene A., De Angelis A., Hosoda T., Chimenti S., Baker M., Limana F., Nurzynska D., Torella D., Rotatori F., Rastaldo R., Musso E., Quaini F., Leri A., Kajstura J., Anversa P. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival . Circ. Res. 2005. 97. P. 663-673. CrossRef PubMed
  46.  
  47. Whittington H.J., Harding I., Stephenson C.I., Bell R., Hausenloy D.J., Mocanu M.M., Yellon D.M. Cardioprotection in the aging, diabetic heart: the loss of protective Akt signalling . Cardiovasc. Res. 2013. 99. P. 694-704. CrossRef PubMed PubMedCentral
  48.  

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