Exogenous sodium hydrosulfide protects against high glucose‑induced injury and inflammation in human umbilical vein endothelial cells by inhibiting necroptosis via the p38 MAPK signaling pathway
| Autor: | Xiaoyong Li, Yan Lin, Wen Wu, Jiaqiong Lin, Zena Huang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Cell Survival MAP Kinase Signaling System Necroptosis Interleukin-1beta necroptosis Sodium hydrosulfide Inflammation sodium hydrosulfide Pharmacology Sulfides p38 MAPK Protective Agents Biochemistry p38 Mitogen-Activated Protein Kinases Umbilical vein Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics medicine Human Umbilical Vein Endothelial Cells Humans Viability assay Molecular Biology Cells Cultured Membrane Potential Mitochondrial Interleukin-6 Tumor Necrosis Factor-alpha Interleukin-8 Articles 030104 developmental biology Glucose Oncology chemistry 030220 oncology & carcinogenesis Receptor-Interacting Protein Serine-Threonine Kinases Molecular Medicine Tumor necrosis factor alpha hyperglycemia medicine.symptom Reactive Oxygen Species Diabetic Angiopathies Signal Transduction |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 |
| Popis: | In recent years hydrogen sulfide (H2S) has demonstrated vasculoprotective effects against cell death, which suggests its promising therapeutic potential for numerous types of disease. Additionally, a protective effect of exogenous H2S in HG‑induced injuries in HUVECs was demonstrated, suggesting a potential protective effect for diabetic vascular complications. The present study aimed to investigate the mechanism accounting for the cytoprotective role of exogenous H2S against high glucose [HG (40 mM glucose)]‑induced injury and inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to HG for 24 h to establish an in vitro model of HG‑induced cytotoxicity. The cells were pretreated with sodium hydrosulfide (NaHS), a donor of H2S, or inhibitors of necroptosis and p38 MAPK prior to the exposure to HG. Cell viability, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), IL‑1β, IL‑6, IL‑8, TNF‑α, phosphorylated‑(p)38 and receptor‑interacting protein 3 (RIP3) expression levels were detected using the indicated methods, including Cell Counting Kit 8, fluorescence detection, western blotting, immunofluorescence assay and ELISAs. The results demonstrated that necroptosis and the p38 MAPK signaling pathway mediated HG‑induced injury and inflammation. Notably, NaHS was discovered to significantly ameliorate p38 MAPK/necroptosis‑mediated injury and inflammation in response to HG, as evidenced by an increase in cell viability, a decrease in ROS generation and loss of MMP, as well as the reduction in the secretion of proinflammatory cytokines. In addition, the upregulated expression of RIP3 induced by HG was repressed by treatment with SB203580, while the HG‑induced upregulation of p‑p38 expression levels were significantly downregulated following the treatment of Nec‑1 and RIP3‑siRNA. In conclusion, the findings of the present study indicated that NaHS may protect HUVECs against HG‑induced injury and inflammation by inhibiting necroptosis via the p38 MAPK signaling pathway, which may represent a promising drug for the therapy of diabetic vascular complications. |
| Databáze: | OpenAIRE |
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