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Effect of overexpression of JAK1 on protection of fucoidan-exposed neurons from glucose-oxygen deprivation/reoxygenation injury |
Hits 277 Download times 293 Received:July 10, 2023 |
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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 Name | Affiliation | E-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 |
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Abstract
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[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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