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Sphingosine kinase 1 promotes cerebral ischemia‐reperfusion injury through inducing ER stress and activating the NF‐κB signaling pathway
Author(s) -
Zhang Mingming,
Zhou Dingzhou,
Ouyang Zhu,
Yu Mengqiang,
Jiang Yugang
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29546
Subject(s) - endoplasmic reticulum , sphingosine , unfolded protein response , sphingosine kinase , inflammation , microbiology and biotechnology , signal transduction , downregulation and upregulation , viability assay , biology , chemistry , apoptosis , immunology , biochemistry , sphingosine 1 phosphate , receptor , gene
Endoplasm reticulum stress and inflammation response have been found to be linked to cerebral ischemia‐reperfusion (IR) injury. Sphingosine kinase 1 (SPHK1) has been reported to be a novel endoplasm reticulum regulator. The aim of our study is to figure out the role of SPHK1 in cerebral IR injury and verify whether it has an ability to regulate inflammation and endoplasm reticulum stress. Hydrogen peroxide was used to induce cerebral IR injury. Enzyme‐linked immunosorbent assay, quantitative polymerase chain reaction, western blots, and immunofluorescence were used to measure the alterations of cell viability, inflammation response, and endoplasm reticulum stress. The results demonstrated that after exposure to hydrogen peroxide, cell viability was reduced whereas SPHK1 expression was significantly elevated. Knockdown of SPHK1 attenuated hydrogen peroxide‐mediated cell death and reversed cell viability. Our data also demonstrated that SPHK1 deletion reduced endoplasm reticulum stress and alleviated inflammation response in hydrogen peroxide‐treated cells. In addition, we also found that SHPK1 modulated endoplasm reticulum stress and inflammation response to through the NF‐κB signaling pathway. Inhibition of NF‐κB signaling pathway has similar results when compared with the cells with SPHK1 deletion. Altogether, our results demonstrated that SPHK1 upregulation, induced by hydrogen peroxide, is responsible for cerebral IR injury through inducing endoplasm reticulum stress and inflammation response in a manner working through the NF‐κB signaling pathway. This finding provides new insight into the molecular mechanism to explain the neuron death induced by cerebral IR injury.