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Effect of overexpression of JAK1 on protection of fucoidan-exposed neurons from glucose-oxygen deprivation/reoxygenation injury
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DOI   10.11656/j.issn.1672-1519.2023.10.18
Key Words   fucoidan;mitophagy;JAK1/STAT3 pathway;PC12 cell;oxidative stress
Author NameAffiliationE-mail
JU Hu Affiliated Hospital of Qinghai University, Xining 810001, China  
ZHAI Ting Affiliated Hospital of Qinghai University, Xining 810001, China  
DAWA Zhuoma High Altitude Medicine Research Center of Qinghai University, Xining 810000, China  
LIU Chuanchuan Affiliated Hospital of Qinghai University, Xining 810001, China 2017900006@qhu.edu.cn 
Abstract
    [Objective] In this study,we investigated whether fucoidan protects neurons from oxidative damage and apoptosis caused by glucose-oxygen deprivation/reoxygenation injury(OGD/RP) by inhibiting JAK1/STAT3 signal pathway. [Methods] A rat model of glucose-oxygen deprivation/reoxygenation injury(OGD/RP) in PC12 cells was established,and the maximum concentration of fucoidan on OGD/RP model was selected by CCK8 method;apoptosis was detected by flow cytometry;ROS levels were determined by reactive oxygen species(ROS) fluorescent probe(DCFH-DA);superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) contents were detected by enzyme-linked immunosorbent assay(ELISA);mitochondrial membrane(MMP) potential changes were determined by JC-1 assay;mitophagy was observed by transmission electron microscopy;mitophagy,apoptosis and JAK1/STAT3 pathway and other related proteins were detected by Western blot. [Results] The 400 mg/kg fucoidan group under OGD/RP injury model was screened by CCK8 to have the strongest cell activity and proliferation ability,which was used for subsequent experimental research. Compared with the OGD/RP group,the contents of SOD and GSH-Px,the quantity of mitophagosomes,the MMP value and the relative expressions of PINK1,Parkin and Lc3II/Lc3I proteins in the cells of the OGD/RP+fucoidan group were increased. Apoptosis rate,apoptosis-related proteins,ROS content and the relative expression of p-JAK1/JAK1,p-STAT/STAT3 proteins were decreased. Compared with the OGD/RP+fucoidan group,the SOD,GSH-Px contents,the quantity of mitophagosomes,MMP value and the relative expressions of PINK1,Parkin and Lc3II/Lc3I proteins of the cells in the OGD/RP+fucoidan+pcDNA3.1-JAK1 group were decreased,while ROS content was increased. [Conclusion] Fucoidan can protect neurons from OGD/RP injury by inhibiting JAK/STAT signal pathway,reducing apoptosis and oxidative damage,and promoting mitophagy.

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