Doxorubicin-induced cardiomyocyte apoptosis: Role of mitofusin 2

Tang, Hongfeng; Tao, Aibin; Song, Jia; Liu, Qian; Wang, Hao; Tao, Rui

doi:10.1016/j.biocel.2017.05.006

Cited by 54 publications

(47 citation statements)

References 26 publications

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“…BioMed Research International studies have proved that cardiomyocyte apoptosis is a vital feature of doxorubicin-induced cardiotoxicity [30]. Consistent with the previous studies [31,32], we observed a significant decrease of heart function in doxorubicin-treated mice, accompanied with an increase of heart/body weight ratio.…”

supporting

confidence: 92%

Dexrazoxane Protects Cardiomyocyte from Doxorubicin-Induced Apoptosis by Modulating miR-17-5p

Ruan

Shen

et al. 2020

BioMed Research International

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The usage of doxorubicin is hampered by its life-threatening cardiotoxicity in clinical practice. Dexrazoxane is the only cardioprotective medicine approved by the FDA for preventing doxorubicin-induced cardiac toxicity. Nevertheless, the mechanism of dexrazoxane is incompletely understood. The aim of our study is to investigate the possible molecular mechanism of dexrazoxane against doxorubicin-induced cardiotoxicity. We established a doxorubicin-induced mouse and cardiomyocyte injury model. Male C57BL/6J mice were randomly distributed into a control group (Con), a doxorubicin treatment group (DOX), a doxorubicin plus dexrazoxane treatment group (DOX+DEX), and a dexrazoxane treatment group (DEX). Echocardiography and histology analyses were performed to evaluate heart function and structure. DNA laddering, qRT-PCR, and Western blot were performed on DOX-treated cardiomyocytes with/without DEX treatment in vitro. Cardiomyocytes were then transfected with miR-17-5p mimics or inhibitors in order to analyze its downstream target. Our results demonstrated that dexrazoxane has a potent effect on preventing cardiac injury induced by doxorubicin in vivo and in vitro by reducing cardiomyocyte apoptosis. MicroRNA plays an important role in cardiovascular diseases. Our data revealed that dexrazoxane could upregulate the expression of miR-17-5p, which plays a cytoprotective role in response to hypoxia by regulating cell apoptosis. Furthermore, the miRNA and protein analysis revealed that miR-17-5p significantly attenuated phosphatase and tensin homolog (PTEN) expression in cardiomyocytes exposed to doxorubicin. Taken together, dexrazoxane might exert a cardioprotective effect against doxorubicin-induced cardiomyocyte apoptosis by regulating the expression of miR-17-5p/PTEN cascade.

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supporting

confidence: 92%

Dexrazoxane Protects Cardiomyocyte from Doxorubicin-Induced Apoptosis by Modulating miR-17-5p

Ruan

Shen

et al. 2020

BioMed Research International

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“…DOX has been widely used in the treatment of human and nonhuman tumors, including leukemia [15], lymphomas, soft tissue sarcomas, and solid cancer [21], e.g., breast tumors, osteosarcomas, Kaposi's sarcoma, Hodgkin's and non-Hodkin's lymphomas [14,22], thyroid and lung carcinomas, stomach, breast, bone, and ovarian cancers [23]. DOX is used for the treatment of solid childhood tumors too, such as non-Hodgkin's lymphomas, Hodgkin's disease, and soft tissue sarcomas [22].…”

Section: Doxorubicin: Anticancer Antibioticsmentioning

confidence: 99%

“…Apoptosis mediated by DOX contributes to heart failure. DOX's main intracellular target is mitochondria, causing mitochondrial damage and ROS elevation, and initiating apoptosis [21]. So, DOX gives rise to degrading contractile proteins [29].…”

Section: Cytotoxic Effect Of Doxorubicin On Noncancerous Tissuesmentioning

confidence: 99%

“…However, limited knowledge of how mitochondrial dysfunction triggers cardiac apoptotic cell death-mediated DOX is still a mystery. Therefore, further studies are needed to increase knowledge [21].…”

Section: Cytotoxic Effect Of Doxorubicin On Noncancerous Tissuesmentioning

confidence: 99%

“…Cardiomyocytes contain high mitochondrial density, and one cardiomyocyte occupies 40-45% of mitochondria [21,34]. The organelle has a function to maintain standard cardiac capacity due to a high-demanding, high-energy substrate for contractile function [21]. DOX accumulates in mitochondria 100 times more than plasma [34].…”

mentioning

confidence: 99%

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Mitochondrial Dysfunction Associated with Doxorubicin

Güven¹,

Sevgiler²,

Taşkın³

2018

Mitochondrial Diseases

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Cancer prevalence is scaling up each year. Anthracycline groups are still the best chemotherapeutic agent. The most popular anticancer drug in the group is doxorubicin (DOX). Unfortunately, DOX has potent toxicity on noncancerous tissues, e.g., heart, kidneys, etc. However, it is well documented that the severest toxicity of the drug affects heart tissue. Of course, some reasons have been suggested why and/or how the heart is so vulnerable to toxicity. The primary mechanism responsible for DOX's cardiospecific toxicity remains unidentified so far; however, mitochondrial dysfunction induced by DOX is now considered one of the leading reasons for DOX's toxicities and undesired side effects. Mitochondrial reactive oxygen production in the heart is a significant contributor to developing mitochondrial dysfunction-exposed DOX based on a variety of evidence. The objective of this review chapter is to critically evaluate and highlight the role of mitochondria in the development of DOX-induced cardiotoxicity. TurkeyMitochondrial Dysfunction Associated with Doxorubicin http://dx.doi.org/10.5772/intechopen.80284 353

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