Diallyl trisulfide attenuates hyperglycemia-induced endothelial apoptosis by inhibition of Drp1-mediated mitochondrial fission

• Published in: Acta diabetologica Vol. 56; no. 11; pp. 1177 - 1189
• Main Authors: Hao, Ying, Liu, Hui-Min, Wei, Xin, Gong, Xue, Lu, Zhao-Yang, Huang, Zhen-Hao
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.11.2019; Springer Nature B.V
• Subjects: Adenosine kinase; Allyl Compounds - pharmacology; AMP; Animal models; Apoptosis; Caspase; Caspase-3; Diabetes; Diallyl trisulfide; Dynamin; Dynamins; Endothelial cells; Flow cytometry; Gene expression; Glucose; Glucose - metabolism; Glucose - toxicity; Glutathione; GTP Phosphohydrolases - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hyperglycemia; Internal Medicine; Kinases; Medicine; Medicine & Public Health; Membrane potential; Metabolic Diseases; Microtubule-Associated Proteins - metabolism; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins - metabolism; Original; Original Article; Protein kinase; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sulfides - pharmacology; Superoxide dismutase; Umbilical vein; High glucose/hyperglycemia; Mitochondrial fission; Diallyl trisulfide; Endothelial cells; Apoptosis; Drp1
• ISSN: 0940-5429; 1432-5233
• DOI: 10.1007/s00592-019-01366-x

Aims Hyperglycemia induces endothelial cell apoptosis and blood vessel damage, while diallyl trisulfide (DATS) has shown cardiovascular protection in animal models and humans. The aim of this study was to investigate the effects of DATS on inhibition of high glucose-induced endothelial cell apoptosis and the underlying molecular events. Methods Human umbilical vein endothelial cells (HUVECs) were incubated with DATS (100 μM) for 30 min and then cultured in high-glucose medium (HG, 33 mM) for 24 h for assessment of apoptosis, glutathione (GSH), reactive oxygen species (ROS), superoxide dismutase (SOD), and gene expression using the terminal deoxyuridine triphosphate nick end labeling (TUNEL), flow cytometry, caspase-3 activity, ROS, SOD, and western blot assays as well as JC-1 and MitoTracker Red staining, respectively. Results DATS treatment significantly inhibited high glucose-induced HUVEC apoptosis by blockage of intracellular and mitochondrial ROS generation, maintenance of the mitochondrial membrane potential, and suppression of high glucose-induced dynamin-related protein 1 (Drp1) expression. Furthermore, DATS blockage of high glucose-induced mitochondrial fission and apoptosis was through adenosine monophosphate-activated protein kinase (AMPK) activation-inhibited Drp1 expression in HUVECs. Conclusions DATS demonstrated the ability to inhibit high glucose-induced HUVEC apoptosis via suppression of Drp1-mediated mitochondrial fission in an AMPK-dependent fashion.