Cryptotanshinone Ameliorates Doxorubicin-Induced Cardiotoxicity by Targeting Akt-GSK-3β-mPTP Pathway In Vitro

被引：40

作者：

Wang, Xiaoping ^{[1
,2
,3
]}

Sun, Qianbin ^{[2
,3
,4
]}

Jiang, Qianqian ^{[2
,3
]}

Jiang, Yanyan ^{[2
,3
,4
]}

Zhang, Yawen ^{[1
,2
,3
]}

Cao, Jing ^{[1
,2
,3
]}

Lu, Linghui ^{[1
,2
,3
]}

Li, Chun ^{[2
,3
,5
]}

Wei, Peng ^{[1
,2
]}

Wang, Qiyan ^{[2
,4
]}

Wang, Yong ^{[1
,2
,3
,4
]}

机构：

[1] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing 100029, Peoples R China

[2] Beijing Key Lab TCM Syndrome & Formula, Beijing 100029, Peoples R China

[3] Beijing Univ Chinese Med, Minist Educ, Key Lab, Beijing 100029, Peoples R China

[4] Beijing Univ Chinese Med, Sch Life Sci, Beijing 100029, Peoples R China

[5] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China

来源：

MOLECULES | 2021年 / 26卷 / 05期

基金：

中国国家自然科学基金;

关键词：

cardiotoxicity; doxorubicin; cryptotanshinone; oxidative stress; apoptosis; mPTP; GSK-3β

D O I：

10.3390/molecules26051460

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cardiotoxicity is one of the main side effects of doxorubicin (Dox) treatment. Dox could induce oxidative stress, leading to an opening of the mitochondrial permeability transition pore (mPTP) and apoptosis in cardiomyocytes. Previous studies have shown that Cryptotanshinone (Cts) has potential cardioprotective effects, but its role in Dox-induced cardiotoxicity (DIC) remains unknown. A Dox-stimulated H9C2 cell model was established. The effects of Cts on cell viability, reactive oxygen species (ROS), superoxide ion accumulation, apoptosis and mitochondrial membrane potential (MMP) were evaluated. Expressions of proteins in Akt-GSK-3 beta pathway were detected by Western blot. An Akt inhibitor was applied to investigate the effects of Cts on the Akt-GSK-3 beta pathway. The effects of Cts on the binding of p-GSK-3 beta to ANT and the formation of the ANT-CypD complex were explored by immunoprecipitation assay. The results showed that Cts could increase cell viability, reduce ROS levels, inhibit apoptosis and protect mitochondrial membrane integrity. Cts increased phosphorylated levels of Akt and GSK-3 beta. After cells were co-treated with an Akt inhibitor, the effects of Cts were abolished. An immunoprecipitation assay showed that Cts significantly increased GSK-3 beta-ANT interaction and attenuated Dox-induced formation of the ANT-CypD complex, thereby inhibiting opening of the mPTP. In conclusion, Cts could ameliorate oxidative stress and apoptosis via the Akt-GSK-3 beta-mPTP pathway.

引用

页数：14

共 36 条

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