Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells

Objective. The present study selected PC12 cells to construct a neuronal injury model induced by glucocorticoids (GC) in vitro, aiming to explore whether the endoplasmic reticulum stress (ERS) PKR-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP-homologous prot...

Full description

Saved in:
Bibliographic Details
Main Authors: Shanyong Yi, Weibo Shi, Min Zuo, Songjun Wang, Rufei Ma, Haitao Bi, Bin Cong, Yingmin Li
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2021/5565671
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849684494788853760
author Shanyong Yi
Weibo Shi
Min Zuo
Songjun Wang
Rufei Ma
Haitao Bi
Bin Cong
Yingmin Li
author_facet Shanyong Yi
Weibo Shi
Min Zuo
Songjun Wang
Rufei Ma
Haitao Bi
Bin Cong
Yingmin Li
author_sort Shanyong Yi
collection DOAJ
description Objective. The present study selected PC12 cells to construct a neuronal injury model induced by glucocorticoids (GC) in vitro, aiming to explore whether the endoplasmic reticulum stress (ERS) PKR-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP-homologous protein (CHOP) and inositol requirement 1 (IRE1)-apoptosis signal regulating kinase 1 (ASK1)-C-Jun amino-terminal kinase (JNK) signaling pathways are associated with the neuronal injury process induced by GC and provide morphological evidence. Methods. Cell models with different doses and different durations of GC exposure were established. The viability of PC12 cells was detected by the CCK-8 assay, and the apoptosis rate of PC12 cells was detected by the flow cytometry assay. The expression of microtubule-associated protein 2 (Map2); glucocorticoids receptor (GR); cellular oncogene fos (C-fos); and ERS-related proteins, glucose-regulated protein 78 (GRP78), p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP, was observed by immunofluorescence staining. Results. The results of immunofluorescence staining showed that PC12 cells abundantly expressed Map2 and GR. The CCK-8 assay revealed that high-concentration GC exposure significantly inhibited the cell viability of PC12 cells. The flow cytometry assay indicated that high-concentration GC exposure significantly increased the apoptosis rate of PC12 cells. Immunofluorescence staining showed that GC exposure significantly increased the expression of C-fos, GRP78, p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP. Treatment with ERS inhibitor 4-phenylbutyric acid (4-PBA) and GR inhibitor RU38486 attenuated related damage and downregulated the expression of the abovementioned proteins. Conclusion. High-concentration GC exposure can significantly inhibit the viability of PC12 cells and induce apoptosis. PERK-ATF4-CHOP and IRE1-ASK1-JNK pathways are involved in the above damage process.
format Article
id doaj-art-bafb7102c35144f1a71aa5d55ad2f0a8
institution DOAJ
issn 2210-7177
2210-7185
language English
publishDate 2021-01-01
publisher Wiley
record_format Article
series Analytical Cellular Pathology
spelling doaj-art-bafb7102c35144f1a71aa5d55ad2f0a82025-08-20T03:23:26ZengWileyAnalytical Cellular Pathology2210-71772210-71852021-01-01202110.1155/2021/55656715565671Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 CellsShanyong Yi0Weibo Shi1Min Zuo2Songjun Wang3Rufei Ma4Haitao Bi5Bin Cong6Yingmin Li7Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, ChinaObjective. The present study selected PC12 cells to construct a neuronal injury model induced by glucocorticoids (GC) in vitro, aiming to explore whether the endoplasmic reticulum stress (ERS) PKR-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP-homologous protein (CHOP) and inositol requirement 1 (IRE1)-apoptosis signal regulating kinase 1 (ASK1)-C-Jun amino-terminal kinase (JNK) signaling pathways are associated with the neuronal injury process induced by GC and provide morphological evidence. Methods. Cell models with different doses and different durations of GC exposure were established. The viability of PC12 cells was detected by the CCK-8 assay, and the apoptosis rate of PC12 cells was detected by the flow cytometry assay. The expression of microtubule-associated protein 2 (Map2); glucocorticoids receptor (GR); cellular oncogene fos (C-fos); and ERS-related proteins, glucose-regulated protein 78 (GRP78), p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP, was observed by immunofluorescence staining. Results. The results of immunofluorescence staining showed that PC12 cells abundantly expressed Map2 and GR. The CCK-8 assay revealed that high-concentration GC exposure significantly inhibited the cell viability of PC12 cells. The flow cytometry assay indicated that high-concentration GC exposure significantly increased the apoptosis rate of PC12 cells. Immunofluorescence staining showed that GC exposure significantly increased the expression of C-fos, GRP78, p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP. Treatment with ERS inhibitor 4-phenylbutyric acid (4-PBA) and GR inhibitor RU38486 attenuated related damage and downregulated the expression of the abovementioned proteins. Conclusion. High-concentration GC exposure can significantly inhibit the viability of PC12 cells and induce apoptosis. PERK-ATF4-CHOP and IRE1-ASK1-JNK pathways are involved in the above damage process.http://dx.doi.org/10.1155/2021/5565671
spellingShingle Shanyong Yi
Weibo Shi
Min Zuo
Songjun Wang
Rufei Ma
Haitao Bi
Bin Cong
Yingmin Li
Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells
Analytical Cellular Pathology
title Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells
title_full Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells
title_fullStr Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells
title_full_unstemmed Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells
title_short Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells
title_sort endoplasmic reticulum stress is involved in glucocorticoid induced apoptosis in pc12 cells
url http://dx.doi.org/10.1155/2021/5565671
work_keys_str_mv AT shanyongyi endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells
AT weiboshi endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells
AT minzuo endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells
AT songjunwang endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells
AT rufeima endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells
AT haitaobi endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells
AT bincong endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells
AT yingminli endoplasmicreticulumstressisinvolvedinglucocorticoidinducedapoptosisinpc12cells