Abstract
This study aims to explore the changes in calcium regulation in the sarcoplasmic reticulum (SR) during doxorubicin (DOX) treatment. Sprague–Dawley rats were treated with intravenous DOX (1.5 mg/kg) twice weekly for 12 treatments. The hemodynamic changes, myocardial oxidative stress, levels of cardiac toxicity markers, and calcium handling of the myocardial SR were observed. When the accumulation of DOX reached 12 mg/kg, (1) heart weight, left ventricular mass, and lung congestion increased significantly, and ascites appeared; (2) SBP, DBP, MAP, +dP/dt, −dP/dt, and LVSP decreased significantly, and LVEDP increased (p < 0.01); (3) the iNOS activity and MDA and NO concentrations significantly increased, while the SOD decreased (p < 0.05 or 0.01); (4) the serum level of the AST, LDH CPK, cTnI, and BNP increased significantly (p < 0.01); (5) during DOX treatment, the rat SR Ca2+ absorption function and Ca2+-stimulated ATPase activity declined dramatically, as did the SERCA2 and phospholamban levels (p < 0.01). As expected, all these changes became evident with DOX accumulation in vivo (p < 0.05 or 0.01). In conclusion, DOX induces SR calcium regulation dysfunction via the decrease of SERCA2 and phospholamban expressions in rats.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 81170125, 81270209), the Science and Technology Commission of Shanghai Municipality (No. 12JC1406400), and the Doctor Innovation Fund of Shanghai Jiao Tong University School of Medicine (BXJ201224).
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Yachen Zhang and Yu Chen contributed equally to this work and should be considered as co-first authors.
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Zhang, Y., Chen, Y., Zhang, M. et al. Doxorubicin Induces Sarcoplasmic Reticulum Calcium Regulation Dysfunction via the Decrease of SERCA2 and Phospholamban Expressions in Rats. Cell Biochem Biophys 70, 1791–1798 (2014). https://doi.org/10.1007/s12013-014-0130-2
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DOI: https://doi.org/10.1007/s12013-014-0130-2