Tetramethylpyrazine attenuates doxorubicin induced cardiotoxicity through 14-3-3γ/Bcl-2
10.12092/j.issn.1009-2501.2021.04.001
- Author:
Xueming DING
1
;
Qiang XU
1
;
Tianpeng CHEN
2
;
Huan HE
2
;
Ming HE
2
Author Information
1. Drug Clinical Trial Institution, The Affiliated Tumor Hospital, Nanchang University
2. Jiangxi Provincial Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University
- Publication Type:Journal Article
- Keywords:
14-3-3γ;
Cardiotoxicity;
Doxorubicin;
Mitochondria;
Tetramethylpyrazine
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2021;26(4):361-367
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effect of tetramethylpyrazine (TMP) on doxorubicin (Dox) induced cardiotoxicity and the role of 14-3-3γ/Bcl-2 protein expression. METHODS: Primary cultured cardiomyocytes were randomly divided into Control group, Dox group, Dox+TMP group and Dox+TMP+pAD/14-3-3γ-shRNA group. After 48 hours, the cell viability was detected by MST, the activity of LDH in culture medium, the activities of Caspase-3, SOD, GSH-Px and the content of MDA were detected; the expression of 14-3-3γ and mitochondrial Bcl-2 was detected by Western blot; ROS generation, mitochondrial membrane potential and mPTP opening were detected by flow cytometry; apoptosis was detected by TUNEL method. RESULTS: After Dox exposed for 48 hours, the viability of cardiomyocytes decreased significantly, the activity of LDH in culture medium increased, the activities of SOD and GSH-Px decreased, the content of MDA increased, ROS generation increased; the mitochondrial membrane potential decreased, mPTP continued to open, caspase-3 activity and apoptosis increased. TMP pretreatment significantly upregulated the expression of 14-3-3γ and mitochondrial Bcl-2, and reversed the above changes simultaneously; pAD/14-3-3γ-shRNA not only downregulated the expression of 14-3-3γ, but also decreased the expression of Bcl-2 in mitochondria. CONCLUSION: TMP pretreatment upregulates the expression of 14-3-3γ and mitochondrial Bcl-2, inhibits oxidative stress, maintains mitochondrial function and reduces Dox induced apoptosis.
