ReferenceID 1113
Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation
Int J Mol Sci
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. PKCd
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- Reference Id
- 1113
- Evidence Id
- 17703
- Core Evidence Id
- 17703
- Source Reference Id
- 2205
- Herb2 Reference Id
- HBREF003002
- Subject Paper Key
- HBIN015205_32283691
- Pubmed Id
- 32283691
- Doi
- 10.3390/ijms21072608
- Paper Title
- Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation
- Paper Abstract
- 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. PKCdelta 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 PKCdelta activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKCdelta mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKCdelta-wild type (WT). Inhibition of PKCdelta by PKCdelta-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKCdelta activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKCdelta-WT plasmids reversed the inhibitory effects of DATS on PKCdelta activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCdelta 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 PKCdelta signaling, suggesting that DATS has potential in diabetic cardiomyopathy (DCM) treatment.
- Journal
- Int J Mol Sci
- Publish Year
- 2020
- Experiment Subject
- rat; age-induced nrvm cells; h9c2 cardiomyoblast cell
- Experiment Type
- Cell Experiment
- Phenotype Related
- Diabetic Cardiomyopathy; Diabetic Mellitus; Mitochondrial Dysfunction
- Paper Title Cn
- Paper Title En
- Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation
- Bilingual Status
- semi_complete