Biomedicine |
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Study on the effect of doxorubicin on expressions of genes encoding myocardial sarcoplasmic reticulum Ca2+ transport proteins and the effect of taurine on myocardial protection in rabbits |
HUANG Xian-mei, ZHU Wei-hua, KANG Man-li |
Children\'s Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China |
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Abstract To investigate the effect of doxorubicin (DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR) Ca2+ transport proteins and the mechanism of taurine (Tau) protecting cardiac muscle cells, 9 rabbits were injected with DOX, 8 rabbits with DOX and Tau, and 9 rabbits with normal saline. Cardiac function, concentration of calcium in cardiomyocytes (Myo[Ca2+]i), activity of SR Ca2+-ATPase(SERCA2a), level of SERCA2a mRNA and Ca2+ released channels(RYR2)mRNA were detected. The left ventricle tissues were observed by electron microscopy. The results showed that cardiac index, left ventricular systolic pressure, activity of SR Ca2+-ATPase and level of SERCA2a mRNA decreased, while Myo[Ca2+]i increased in DOX-treated rabbits. DOX could not affect the level of RYR2 mRNA. Tau intervention could alleviate the increase of left ventricular diastolic pressure, Myo[Ca2+]i and the decrease of SERCA2a mRNA induced by doxorubicin. The results suggested that downregulation of SERCA2a gene expression was an important mechanism of DOX-induced cardiomyopathy and that Tau could partially improve the heart function by reducing calcium overload and alleviating downregulation of SERCA2a mRNA.
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Received: 28 December 2001
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