Downregulation of doxorubicin-induced myocardial apoptosis accompanies postnatal heart maturation.

American Journal of Physiology. Heart and Circulatory Physiology
Jianjian ShiLei Wei

Abstract

Doxorubicin is a highly effective chemotherapeutic agent used for treating a wide spectrum of tumors, but its usage is limited because of its dose-dependent cardiotoxicity, especially in pediatric patients. Accumulating evidence indicates that caspase-dependent apoptosis contributes to the cardiotoxicity of doxorubicin. However, less attention has been paid to the effects of age on doxorubicin-induced apoptosis signaling in myocardium. This study focused on investigating differential apoptotic sensitivity between neonatal and adult myocardium, in particular, between neonatal and adult cardiomyocytes in vivo. Our results show that caspase-3 activity in normal mouse hearts decreased by ≥ 20-fold within the first 3 wk after birth, associated with a rapid downregulation in the expression of key proapoptotic proteins in intrinsic and extrinsic pathways. This rapid downregulation of caspase-3 activity was confirmed by immunostaining for cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP-mediated nick-end label staining. Doxorubicin treatment induced a dose-dependent increase in caspase-3 activity and apoptosis in neonatal mouse hearts, and both caspase-8 and caspase-9 activations were involved. Using transgenic mice wit...Continue Reading

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Citations

Apr 11, 2013·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Ronald G SchwartzEugene Storozynsky
Feb 9, 2013·Cell Death & Disease·Jianjian ShiLei Wei
Nov 26, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Francesco CorradiRaffaele De Caterina
Dec 6, 2012·Canadian Journal of Physiology and Pharmacology·Jian-Zhe LiXiao-Min Dong
Aug 9, 2017·Cancer Chemotherapy and Pharmacology·Mohamed M Abdel-DaimAmal A M Ahmed
Mar 9, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jianjian ShiLei Wei
Oct 15, 2013·Fundamental & Clinical Pharmacology·Azhar RashikhAbul Kalam Najmi
Dec 10, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Cynthia KankeuHeinrich J Huber
Aug 31, 2018·Biology of Sex Differences·Becky MeinersBeshay N Zordoky
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lei WeiJianjian Shi

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