{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:05:59Z","timestamp":1786705559822,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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. PKC\u03b4 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 PKC\u03b4 activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKC\u03b4 mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKC\u03b4-wild type (WT). Inhibition of PKC\u03b4 by PKC\u03b4-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKC\u03b4 activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKC\u03b4-WT plasmids reversed the inhibitory effects of DATS on PKC\u03b4 activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKC\u03b4 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 PKC\u03b4 signaling, suggesting that DATS has potential in diabetic cardiomyopathy (DCM) treatment.<\/jats:p>","DOI":"10.3390\/ijms21072608","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T14:42:03Z","timestamp":1586443323000},"page":"2608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKC\u03b4 Activation"],"prefix":"10.3390","volume":"21","author":[{"given":"Dennis Jine-Yuan","family":"Hsieh","sequence":"first","affiliation":[{"name":"School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-2240","authenticated-orcid":false,"given":"Shang-Chuan","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-You","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viswanadha Vijaya","family":"Padma","sequence":"additional","affiliation":[{"name":"Translational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641046, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-0411","authenticated-orcid":false,"given":"Chih-Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan"},{"name":"Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"},{"name":"Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Biotechnology, Asia University, Taichung 413, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-2240","authenticated-orcid":false,"given":"Wei-Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e121","DOI":"10.1161\/STROKEAHA.115.008097","article-title":"Organizational update: The world health organization global status report on noncommunicable diseases 2014; one more landmark step in the combat against stroke and vascular disease","volume":"46","author":"Mendis","year":"2015","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S","article-title":"Definition, diagnosis and classification of diabetes mellitus and its complications. 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