Protective role of PERK-eIF2α-ATF4 pathway in chronic renal failure induced injury of rat hippocampal neurons.

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Title: Protective role of PERK-eIF2α-ATF4 pathway in chronic renal failure induced injury of rat hippocampal neurons.
Authors: Chen, Qi (AUTHOR), Min, Jingjing (AUTHOR), Zhu, Ming (AUTHOR), Shi, Zhanqin (AUTHOR), Chen, Pingping (AUTHOR), Ren, Lingyan (AUTHOR), Wang, Xiaoyi (AUTHOR)
Source: International Journal of Neuroscience. Feb2023, Vol. 133 Issue 2, p123-132. 10p.
Subjects: Chronic kidney failure, Hippocampus (Brain), Neurons, Xanthine oxidase, Endoplasmic reticulum, Reactive oxygen species, Serum
Abstract: Chronic renal failure (CRF) is associated with impairment of hippocampal neurons. This study investigated the effect of PERK-eIF2α-ATF4 pathway in CRF. Rat CRF model was established and rat hippocampal neurons were separated. Xanthine Oxidase method, fluorescence spectrophotometry and flow cytometry were applied to detect superoxide dismutase (SOD) content, reactive oxygen species (ROS) level and apoptosis in hippocampal neurons, respectively. The levels of phosphorylated (p)-PERK, phosphorylated (p)-eIF2α, CHOP, Bax, C-Caspase-3 and Bcl-2 in rats were measured using Western blot. Then, the neurotoxicity of serum from CRF rats was assessed in rat hippocampal neurons after treatment with rat CRF serum and transfection with or without PERK overexpression or knockdown plasmid. SOD activity was reduced, while ROS level and apoptosis rate were increased in hippocampal tissues of CRF rats. PERK-eIF2α-ATF4 and apoptosis pathways were activated in CRF rats. Cells treated with serum from CRF rats showed increases in apoptosis rate and LDH and ROS levels, and decreases in cell viability and SOD activity. However, overexpressed PERK could reverse the cytotoxic effect of serum from CRF rats. PERK overexpression could enhance the activation of PERK-eIF2α-ATF4 pathway in hippocampal neurons induced by serum from CRF rats. Furthermore, PERK overexpression could alleviate the increases in CHOP, Bax, C-Caspase-3 expressions and the reduction of Bcl-2 expression in hippocampal neurons induced by serum from CRF rats. PERK-eIF2α-ATF4 pathway induced by increased endoplasmic reticulum stress may alleviate CRF-induced hippocampal neuronal damage. [ABSTRACT FROM AUTHOR]
Copyright of International Journal of Neuroscience is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Protective role of PERK-eIF2α-ATF4 pathway in chronic renal failure induced injury of rat hippocampal neurons.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Chen%2C+Qi%22">Chen, Qi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Min%2C+Jingjing%22">Min, Jingjing</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhu%2C+Ming%22">Zhu, Ming</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shi%2C+Zhanqin%22">Shi, Zhanqin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Pingping%22">Chen, Pingping</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ren%2C+Lingyan%22">Ren, Lingyan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Xiaoyi%22">Wang, Xiaoyi</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Neuroscience%22">International Journal of Neuroscience</searchLink>. Feb2023, Vol. 133 Issue 2, p123-132. 10p.
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  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Chronic+kidney+failure%22">Chronic kidney failure</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Neurons%22">Neurons</searchLink><br /><searchLink fieldCode="DE" term="%22Xanthine+oxidase%22">Xanthine oxidase</searchLink><br /><searchLink fieldCode="DE" term="%22Endoplasmic+reticulum%22">Endoplasmic reticulum</searchLink><br /><searchLink fieldCode="DE" term="%22Reactive+oxygen+species%22">Reactive oxygen species</searchLink><br /><searchLink fieldCode="DE" term="%22Serum%22">Serum</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Chronic renal failure (CRF) is associated with impairment of hippocampal neurons. This study investigated the effect of PERK-eIF2α-ATF4 pathway in CRF. Rat CRF model was established and rat hippocampal neurons were separated. Xanthine Oxidase method, fluorescence spectrophotometry and flow cytometry were applied to detect superoxide dismutase (SOD) content, reactive oxygen species (ROS) level and apoptosis in hippocampal neurons, respectively. The levels of phosphorylated (p)-PERK, phosphorylated (p)-eIF2α, CHOP, Bax, C-Caspase-3 and Bcl-2 in rats were measured using Western blot. Then, the neurotoxicity of serum from CRF rats was assessed in rat hippocampal neurons after treatment with rat CRF serum and transfection with or without PERK overexpression or knockdown plasmid. SOD activity was reduced, while ROS level and apoptosis rate were increased in hippocampal tissues of CRF rats. PERK-eIF2α-ATF4 and apoptosis pathways were activated in CRF rats. Cells treated with serum from CRF rats showed increases in apoptosis rate and LDH and ROS levels, and decreases in cell viability and SOD activity. However, overexpressed PERK could reverse the cytotoxic effect of serum from CRF rats. PERK overexpression could enhance the activation of PERK-eIF2α-ATF4 pathway in hippocampal neurons induced by serum from CRF rats. Furthermore, PERK overexpression could alleviate the increases in CHOP, Bax, C-Caspase-3 expressions and the reduction of Bcl-2 expression in hippocampal neurons induced by serum from CRF rats. PERK-eIF2α-ATF4 pathway induced by increased endoplasmic reticulum stress may alleviate CRF-induced hippocampal neuronal damage. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of International Journal of Neuroscience is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1080/00207454.2021.1896503
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      – Code: eng
        Text: English
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        PageCount: 10
        StartPage: 123
    Subjects:
      – SubjectFull: Chronic kidney failure
        Type: general
      – SubjectFull: Hippocampus (Brain)
        Type: general
      – SubjectFull: Neurons
        Type: general
      – SubjectFull: Xanthine oxidase
        Type: general
      – SubjectFull: Endoplasmic reticulum
        Type: general
      – SubjectFull: Reactive oxygen species
        Type: general
      – SubjectFull: Serum
        Type: general
    Titles:
      – TitleFull: Protective role of PERK-eIF2α-ATF4 pathway in chronic renal failure induced injury of rat hippocampal neurons.
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            NameFull: Chen, Qi
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            NameFull: Min, Jingjing
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            NameFull: Zhu, Ming
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            NameFull: Shi, Zhanqin
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            NameFull: Chen, Pingping
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            – D: 01
              M: 02
              Text: Feb2023
              Type: published
              Y: 2023
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