About this Biochemistry, Genetics and Molecular Biology article

Doxorubicin downregulates autophagy to promote apoptosis-induced dilated cardiomyopathy via regulating the AMPK/mTOR pathway by Sheng Zhang; Xueping Wei; Haijin Zhang; Youping Wu; Junsong Jing; Rongrong Huang; Ting Zhou; Jingjin Hu; Yueguo Wu; Yuanyuan Li; Zhenqiang You is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

The broad-spectrum antineoplastic drug doxorubicin (DOX) has one of the most serious chronic side effects on the heart, dilated cardiomyopathy, but the precise molecular mechanisms underlying disease progression subsequent to long latency periods remain puzzling. Here, we established a model of DOX-induced dilated cardiomyopathy. In a cardiac cytology exploration, we found that differentially expressed genes in the KEGG signaling pathway enrichment provided a novel complex network of mTOR bridging autophagy and oxidative stress. Validation results showed that DOX caused intracellular reactive oxygen species accumulation in cardiomyocytes, disrupted mitochondria, led to imbalanced intracellular energy metabolism, and triggered cardiomyocyte apoptosis. Apoptosis showed a negative correlation with DOX-regulated cardiomyocyte autophagy. To evaluate whether the inhibition of mTOR could upregulate autophagy to protect cardiomyocytes, we used rapamycin to restore autophagy depressed by DOX. Rapamycin increased cardiomyocyte survival by easing the autophagic flux blocked by DOX. In addition, rapamycin reduced oxidative stress, prevented mitochondrial damage, and restored energy metabolic h

Author

Sheng Zhang; Xueping Wei; Haijin Zhang; Youping Wu; Junsong Jing; Rongrong Huang; Ting Zhou; Jingjin Hu; Yueguo Wu; Yuanyuan Li; Zhenqiang You

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)