A novel damage mechanism: Contribution of the interaction between necroptosis and ROS to high glucose-induced injury and inflammation in H9c2 cardiac cells

Abstract

Recently, a novel mechanism known as 'programmed necrosis' or necroptosis has been shown to be another important mechanism of cell death in the heart. In this study, we investigated the role of necroptosis in high glucose (HG)-induced injury and inflammation, as well as the underlying mechanisms. In particular, we focused on the interaction between necroptosis and reactive oxygen species (ROS) in H9c2 cardiac cells. Our results demonstrated that the exposure of H9c2 cardiac cells to 35 mM glucose (HG) markedly enhanced the expression level of receptor-interacting protein 3 (RIP3), a kinase which promotes necroptosis. Importantly, co-treatment of the cells with 100 µM necrostatin-1 (a specific inhibitor of necroptosis) and HG for 24 h attenuated not only the increased expression level of RIP3, but also the HG-induced injury and inflammation, as evidenced by an increase in cell viability, a decrease in ROS generation, the attenuation of the dissipation of mitochondrial membrane potential and a decrese in the secretion levels of inflammatory cytokines, i.e., interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Furthermore, treatment of the cells with 1 mM N-acetyl‑L‑cysteine (a scavenger of ROS) for 60 min prior to exposure to HG significantly reduced the HG-induced increase in the RIP3 expression level, as well as the injury and inflammatory response described above. Taken together, the findings of this study clearly demonstrate a novel damage mechanism involving the positive interaction between necroptosis and ROS attributing to HG-induced injury and inflammation in H9c2 cardiac cells.

E4An Ultrastructural Study by Transmission Electron Microscope of Exocrine Pancreatic Cells in Diabetic Rats Treated with Herbal Combination

“…The degenerative alterations in pancreatic acini in diabetic-induced rats may due to increased ROS production which are able to oxidation alteration and destruction of lipid in cellular membranes, particularly highly unsaturated fatty acids, by way of lipid peroxidation, result in suppression of the synthesis of protein and fragility of the zymogen granules (36). Particularly, production of ROS has been revealed to be influential in the etiology of diabetes by acting at the following various levels: 1) impairing uptake of glucose and pathways of insulin signaling (37, 2) modifying lipid metabolism and metabolic parameters (38,3) immune activation and raising inflammatory response (39) and (4) Both apoptosis and necroptosis that may culminate in tissue injuries in the kidneys, heart, retina, and nervous system (40).…”

Programmed necrosis in cardiomyocytes: mitochondria, death receptors and beyond

“…These changes contributed to the elucidation of cholesterol‐induced necroptosis (Chtourou et al ., ). Furthermore, it was confirmed that the positive interaction between necroptosis and ROS is due to injury induced by high glucose levels and inflammation in H9C2 cardiac cells (Liang et al ., ).…”

Cellular death, reactive oxygen species (ROS) and diabetic complications

“…Acute or chronic high glucose in diabetes increases the production of ROS and activates apoptosis in the β-cells 15 . Both apoptosis and necroptosis have important roles in the progression of diabetic complications and they may culminate in tissue injuries in the heart, retina, kidneys, and nervous system 16 , 17 .…”