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Gene Review

Atp2a2  -  ATPase, Ca++ transporting, cardiac muscle,...

Rattus norvegicus

Synonyms: Calcium pump 2, Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform, Endoplasmic reticulum class 1/2 Ca(2+) ATPase, SERCA2, SR Ca(2+)-ATPase 2, ...
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Disease relevance of Atp2a2


High impact information on Atp2a2

  • The Ca2+ ATPase of the sarcoplasmic reticulum (SERCA2) plays a dominant role in lowering cytoplasmic calcium levels during cardiac relaxation and reduction of its activity has been linked to delayed diastolic relaxation in hypothyroid and failing hearts [4].
  • Similar results were obtained for the contractile performance of myocytes isolated from a separate line (CJ2) of homozygous SERCA2 transgenic mice [4].
  • To determine the contractile alterations resulting from increased SERCA2 expression, we generated transgenic mice overexpressing a rat SERCA2 transgene [4].
  • Furthermore, cardiac function measured in vivo, demonstrated significantly accelerated contraction and relaxation in SERCA2 transgenic mice that were further augmented in both groups with isoproterenol administration [4].
  • In isolated papillary muscle from SERCA2 transgenic mice, the time to half maximum postrest potentiation was significantly shorter than in negative littermates [4].

Chemical compound and disease context of Atp2a2


Biological context of Atp2a2


Anatomical context of Atp2a2

  • Remarkably, the SLN/(SERCA1 + SERCA2) mRNA ratio in normal cardiac muscle (0.96) was nearly the same as in diaphragm, but in EDL it amounted to only 0.05 that in diaphragm [15].
  • Sarcoplasmic reticulum calcium cycling is determined in part by the ratio of SERCA2 to PLB [16].
  • Thyroid hormone exerts positive inotropic effects on the heart mediated in part by its regulation of calcium transporter proteins, including sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2), phospholamban (PLB), and Na(+)/Ca(2+) exchanger (NCX) [16].
  • Pulmonary trunk banding resulted in an induction of ANP mRNA, a moderate increase in collagenIII alpha1 mRNA and a decrease in SERCA2 and PLB mRNA levels in both the left and right ventricles, but changes were most pronounced in the myocardium surrounding the RV cavity [17].
  • These results imply that the SERCA2 isoform controls Ca2+ sequestration into the endoplasmic reticulum in most classes of retinal neuron [1].

Associations of Atp2a2 with chemical compounds

  • As a result the relative proportion of SERCA2 mRNA was increased from 43 +/- 7 % in control diaphragm to 52 +/- 4 % after triamcinolone treatment (P < 0.05) [15].
  • In primary cultured neonatal rat cardiac myocytes, treatment with either carvedilol or its beta-receptor inactive metabolite, BM910228, attenuated the hydrogen peroxide-mediated decrease in SERCA2 mRNA and protein levels, while metoprolol, a pure beta-blocker, had no effect [12].
  • This hypothesis predicts that improved SERCA2 function would provide protection from cardiotoxic effects of anthracycline administration [18].
  • Doxorubicin was administered (1.7 mg/kg three times weekly; cumulative dose of 20 mg/kg) to 10 transgenic mice that overexpressed SERCA2 and to 10 isogenic littermates [18].
  • In this study we have shown that the decrease in SERCA2 gene expression (normalized by poly(A)+ mRNA or 18 S rRNA) in rats with 8 wk of aortic constriction was prevented by treatment with etomoxir, an inhibitor of carnitine palmitoyltransferase 1 [14].

Regulatory relationships of Atp2a2


Other interactions of Atp2a2

  • This reduction was accounted for by a relatively larger decrease in the SERCA1 mRNA (-69 %, P < 0.05) whilst the decrease in SERCA2 mRNA (-49 %, P = 0.09) did not reach statistical significance [15].
  • Similar beneficial effects of etomoxir treatment were also evident when the gene expression for SR SERCA2, PLP, and CRC in the hypertrophied heart was normalized with respect to mRNA for GAPDH [14].
  • We investigated the expression of the SERCA2 and SERCA3 isozymes in PC12 cells exposed to agents interfering with different aspects of the posttranslational protein processing within the ER, thereby activating the ER stress-induced unfolded protein response (UPR) [23].
  • Although beta-MHC and Kv1.5 mRNA content was returned to control levels, alpha-MHC and SERCA2 were unresponsive to T(3) at replacement doses, and only at higher doses of T(3) was alpha-MHC mRNA returned to control values [24].
  • In this study, we investigated the effects of these cytokines (LIF & IL-6) on the regulation of SERCA2 levels in cardiac myocytes [22].

Analytical, diagnostic and therapeutic context of Atp2a2


  1. Serca isoform expression in the mammalian retina. Krizaj, D. Exp. Eye Res. (2005) [Pubmed]
  2. Isoenzyme-selective regulation of SERCA2 gene expression by protein kinase C in neonatal rat ventricular myocytes. Porter, M.J., Heidkamp, M.C., Scully, B.T., Patel, N., Martin, J.L., Samarel, A.M. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  3. Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes. Ahlers, B.A., Song, J., Wang, J., Zhang, X.Q., Carl, L.L., Tadros, G.M., Rothblum, L.I., Cheung, J.Y. J. Appl. Physiol. (2005) [Pubmed]
  4. Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation. He, H., Giordano, F.J., Hilal-Dandan, R., Choi, D.J., Rockman, H.A., McDonough, P.M., Bluhm, W.F., Meyer, M., Sayen, M.R., Swanson, E., Dillmann, W.H. J. Clin. Invest. (1997) [Pubmed]
  5. Transcription factor Sp1 regulates SERCA2 gene expression in pressure-overloaded hearts: a study using in vivo direct gene transfer into living myocardium. Takizawa, T., Arai, M., Tomaru, K., Koitabashi, N., Baker, D.L., Periasamy, M., Kurabayashi, M. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  6. Influences of increased expression of the Ca2+ ATPase of the sarcoplasmic reticulum by a transgenic approach on cardiac contractility. Dillmann, W.H. Ann. N. Y. Acad. Sci. (1998) [Pubmed]
  7. Senescent heart compared with pressure overload-induced hypertrophy. Assayag, P., Charlemagne, D., de Leiris, J., Boucher, F., Valère, P.E., Lortet, S., Swynghedauw, B., Besse, S. Hypertension (1997) [Pubmed]
  8. The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene promoter activity is decreased in response to severe left ventricular pressure-overload hypertrophy in rat hearts. Aoyagi, T., Yonekura, K., Eto, Y., Matsumoto, A., Yokoyama, I., Sugiura, S., Momomura, S., Hirata, Y., Baker, D.L., Periasamy, M. J. Mol. Cell. Cardiol. (1999) [Pubmed]
  9. Phorbol myristate acetate-induced hypertrophy of neonatal rat cardiac myocytes is associated with decreased sarcoplasmic reticulum Ca2+ ATPase (SERCA2) gene expression and calcium reuptake. Hartong, R., Villarreal, F.J., Giordano, F., Hilal-Dandan, R., McDonough, P.M., Dillmann, W.H. J. Mol. Cell. Cardiol. (1996) [Pubmed]
  10. Phospholamban ablation by RNA interference increases Ca2+ uptake into rat cardiac myocyte sarcoplasmic reticulum. Watanabe, A., Arai, M., Yamazaki, M., Koitabashi, N., Wuytack, F., Kurabayashi, M. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  11. Sp1 and Sp3 transcription factors are required for trans-activation of the human SERCA2 promoter in cardiomyocytes. Brady, M., Koban, M.U., Dellow, K.A., Yacoub, M., Boheler, K.R., Fuller, S.J. Cardiovasc. Res. (2003) [Pubmed]
  12. Carvedilol effectively blocks oxidative stress-mediated downregulation of sarcoplasmic reticulum Ca2+-ATPase 2 gene transcription through modification of Sp1 binding. Koitabashi, N., Arai, M., Tomaru, K., Takizawa, T., Watanabe, A., Niwano, K., Yokoyama, T., Wuytack, F., Periasamy, M., Nagai, R., Kurabayashi, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. Sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) gene silencing and remodeling of the Ca2+ signaling mechanism in cardiac myocytes. Seth, M., Sumbilla, C., Mullen, S.P., Lewis, D., Klein, M.G., Hussain, A., Soboloff, J., Gill, D.L., Inesi, G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  14. Modification of sarcoplasmic reticulum gene expression in pressure overload cardiac hypertrophy by etomoxir. Zarain-Herzberg, A., Rupp, H., Elimban, V., Dhalla, N.S. FASEB J. (1996) [Pubmed]
  15. Corticosteroids decrease mRNA levels of SERCA pumps, whereas they increase sarcolipin mRNA in the rat diaphragm. Gayan-Ramirez, G., Vanzeir, L., Wuytack, F., Decramer, M. J. Physiol. (Lond.) (2000) [Pubmed]
  16. Differential regulation of SR calcium transporters by thyroid hormone in rat atria and ventricles. Shenoy, R., Klein, I., Ojamaa, K. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  17. Changing patterns of gene expression in the pulmonary trunk-banded rat heart. LekanneDeprez, R.H., van den Hoff, M.J., de Boer, P.A., Ruijter, P.M., Maas, A.A., Chamuleau, R.A., Lamers, W.H., Moorman, A.F. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  18. Anthracycline cardiotoxicity in transgenic mice overexpressing SR Ca2+-ATPase. Burke, B.E., Olson, R.D., Cusack, B.J., Gambliel, H.A., Dillmann, W.H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. Multiple Sp1 binding sites in the cardiac/slow twitch muscle sarcoplasmic reticulum Ca2+-ATPase gene promoter are required for expression in Sol8 muscle cells. Baker, D.L., Dave, V., Reed, T., Periasamy, M. J. Biol. Chem. (1996) [Pubmed]
  20. SERCA pump isoform expression in endothelium of veins and arteries: every endothelium is not the same. Khan, I., Sandhu, V., Misquitta, C.M., Grover, A.K. Mol. Cell. Biochem. (2000) [Pubmed]
  21. The antidiabetic agent rosiglitazone upregulates SERCA2 and enhances TNF-alpha- and LPS-induced NF-kappaB-dependent transcription and TNF-alpha-induced IL-6 secretion in ventricular myocytes. Shah, R.D., Gonzales, F., Golez, E., Augustin, D., Caudillo, S., Abbott, A., Morello, J., McDonough, P.M., Paolini, P.J., Shubeita, H.E. Cell. Physiol. Biochem. (2005) [Pubmed]
  22. Leukemia Inhibitory Factor and Interleukin-6 downregulate sarcoplasmic reticulum Ca2+ ATPase (SERCA2) in cardiac myocytes. Villegas, S., Villarreal, F.J., Dillmann, W.H. Basic Res. Cardiol. (2000) [Pubmed]
  23. The sarco/endoplasmic reticulum calcium-ATPase 2b is an endoplasmic reticulum stress-inducible protein. Caspersen, C., Pedersen, P.S., Treiman, M. J. Biol. Chem. (2000) [Pubmed]
  24. Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat. Ojamaa, K., Kenessey, A., Shenoy, R., Klein, I. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  25. Expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase slow (SERCA2) isoform in regenerating rat soleus skeletal muscle depends on nerve impulses. Germinario, E., Esposito, A., Midrio, M., Betto, R., Danieli-Betto, D. Exp. Physiol. (2002) [Pubmed]
  26. Isoforms of endoplasmic reticulum Ca(2+)-ATPase are differentially expressed in normal and diabetic islets of Langerhans. Váradi, A., Molnár, E., Ostenson, C.G., Ashcroft, S.J. Biochem. J. (1996) [Pubmed]
  27. Altered cellular calcium regulatory systems in a rat model of cirrhotic cardiomyopathy. Ward, C.A., Liu, H., Lee, S.S. Gastroenterology (2001) [Pubmed]
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