Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation
Chronic high-glucose exposure results in the production of advanced glycation end-products (AGEs) leading to reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. PKCδ activation leading to ROS production and mitochondrial dysfunction involved in...
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doaj-d3b0ffeaaef14ba5a9efeef4fb02130f2020-11-25T02:26:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01212608260810.3390/ijms21072608Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ ActivationDennis Jine-Yuan Hsieh0Shang-Chuan Ng1Ren-You Zeng2Viswanadha Vijaya Padma3Chih-Yang Huang4Wei-Wen Kuo5School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, TaiwanDepartment of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, TaiwanDepartment of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, TaiwanTranslational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641046, Tamil Nadu, IndiaGraduate Institute of Biomedical Sciences, China Medical University, Taichung 404, TaiwanDepartment of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, TaiwanChronic high-glucose exposure results in the production of advanced glycation end-products (AGEs) leading to reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. PKCδ activation leading to ROS production and mitochondrial dysfunction involved in AGE-induced cardiomyocyte apoptosis was reported in our previous study. Diallyl trisulfide (DATS) is a natural cytoprotective compound under various stress conditions. In this study, the cardioprotective effect of DATS against rat streptozotocin (STZ)-induced diabetic mellitus (DM) and AGE-induced H9c2 cardiomyoblast cell/neonatal rat ventricular myocyte (NRVM) damage was assessed. We observed that DATS treatment led to a dose-dependent increase in cell viability and decreased levels of ROS, inhibition of PKCδ activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKCδ mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKCδ-wild type (WT). Inhibition of PKCδ by PKCδ-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKCδ activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKCδ-WT plasmids reversed the inhibitory effects of DATS on PKCδ activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCδ activation. Similar results were observed in AGE-induced NRVM cells and STZ-treated DM rats following DATS administration. Taken together, our results suggested that DATS reduced AGE-induced cardiomyocyte apoptosis by eliminating ROS and downstream PKCδ signaling, suggesting that DATS has potential in diabetic cardiomyopathy (DCM) treatment.https://www.mdpi.com/1422-0067/21/7/2608DATSAGEPKCδcardiomyocyteapoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dennis Jine-Yuan Hsieh Shang-Chuan Ng Ren-You Zeng Viswanadha Vijaya Padma Chih-Yang Huang Wei-Wen Kuo |
spellingShingle |
Dennis Jine-Yuan Hsieh Shang-Chuan Ng Ren-You Zeng Viswanadha Vijaya Padma Chih-Yang Huang Wei-Wen Kuo Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation International Journal of Molecular Sciences DATS AGE PKCδ cardiomyocyte apoptosis |
author_facet |
Dennis Jine-Yuan Hsieh Shang-Chuan Ng Ren-You Zeng Viswanadha Vijaya Padma Chih-Yang Huang Wei-Wen Kuo |
author_sort |
Dennis Jine-Yuan Hsieh |
title |
Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation |
title_short |
Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation |
title_full |
Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation |
title_fullStr |
Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation |
title_full_unstemmed |
Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation |
title_sort |
diallyl trisulfide (dats) suppresses age-induced cardiomyocyte apoptosis by targeting ros-mediated pkcδ activation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-04-01 |
description |
Chronic high-glucose exposure results in the production of advanced glycation end-products (AGEs) leading to reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. PKCδ activation leading to ROS production and mitochondrial dysfunction involved in AGE-induced cardiomyocyte apoptosis was reported in our previous study. Diallyl trisulfide (DATS) is a natural cytoprotective compound under various stress conditions. In this study, the cardioprotective effect of DATS against rat streptozotocin (STZ)-induced diabetic mellitus (DM) and AGE-induced H9c2 cardiomyoblast cell/neonatal rat ventricular myocyte (NRVM) damage was assessed. We observed that DATS treatment led to a dose-dependent increase in cell viability and decreased levels of ROS, inhibition of PKCδ activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKCδ mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKCδ-wild type (WT). Inhibition of PKCδ by PKCδ-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKCδ activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKCδ-WT plasmids reversed the inhibitory effects of DATS on PKCδ activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCδ activation. Similar results were observed in AGE-induced NRVM cells and STZ-treated DM rats following DATS administration. Taken together, our results suggested that DATS reduced AGE-induced cardiomyocyte apoptosis by eliminating ROS and downstream PKCδ signaling, suggesting that DATS has potential in diabetic cardiomyopathy (DCM) treatment. |
topic |
DATS AGE PKCδ cardiomyocyte apoptosis |
url |
https://www.mdpi.com/1422-0067/21/7/2608 |
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