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

Liang,Weijie; Chen,Meiji; Zheng,Dongdan; He,Jieyi; Song,Mingcai; Mo,Liqiu; Feng,Jianqiang; Lan,Jun

doi:10.3892/ijmm.2017.3006

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

Authors:
- Weijie Liang
- Meiji Chen
- Dongdan Zheng
- Jieyi He
- Mingcai Song
- Liqiu Mo
- Jianqiang Feng
- Jun Lan
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Affiliations: Department of Cardiology, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, P.R. China, Department of Pediatrics, Huangpu Division of The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510700, P.R. China, Department of Cardiac Care Unit, Huangpu Division of The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510700, P.R. China, Department of Anesthesiology, Huangpu Division of The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510700, P.R. China, Department of Cardiology, The Third People's Hospital of Dongguan, Dongguan, Guangdong 523326, P.R. China
Published online on: May 29, 2017 https://doi.org/10.3892/ijmm.2017.3006
Pages: 201-208

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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.

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