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.
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 Ca(2+)-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 Ca(2+)-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.
Huang
Xian-mei
XM
Children' s Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. hxianmei@hotmail.com
Zhu
Wei-hua
WH
Kang
Man-li
ML
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000252:Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013654:Taurine / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D013654:Taurine; D004317:Doxorubicin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases