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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.

Abstract：

: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.

journal_name

Mol Med Rep

journal_title

Molecular medicine reports

authors

Lin J,Li X,Lin Y,Huang Z,Wu W

doi

10.3892/mmr.2020.11706

subject

Has Abstract

pub_date

2021-01-01 00:00:00

issue

eissn

1791-2997

issn

1791-3004

pii

journal_volume

pub_type

杂志文章

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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.