Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
October-2021 Volume 22 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2021 Volume 22 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis

  • Authors:
    • Yu Gao
    • Libo Li
    • Jianbai Yu
    • Zhanwei Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410007, P.R. China
    Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1189
    |
    Published online on: August 17, 2021
       https://doi.org/10.3892/etm.2021.10623
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The endoplasmic reticulum stress (ERS) response serves an important role in cerebral ischemia‑reperfusion injury (CIRI). However, to the best of the our knowledge, the effect of rosuvastatin on the ERS response in CIRI has not yet been studied. In the present study, the effect of rosuvastatin on cell damage in CIRI was investigated; furthermore, the effect of rosuvastatin on the ERS response was explored. Firstly, a hypoxia/reoxygenation (H/R)‑induced cell damage model was established in PC12 cells. Cell viability was subsequently detected by a Cell Counting Kit‑8 assay. A lactate dehydrogenase kit was used to detect cytotoxicity. TUNEL assay was then used to measure the extent of cell apoptosis, and western blotting was used to analyze the expression levels of the apoptosis‑associated proteins Bax, Bcl‑2, cleaved caspase‑3 and cleaved caspase‑9. In addition, western blotting was used to detect the expression levels of ERS‑associated proteins, including phosphorylated (p)‑protein kinase R‑like endoplasmic reticulum kinase (PERK), p‑eukaryotic initiation factor 2α and other proteins. Treatment with rosuvastatin led to an increased activity of H/R‑induced PC12 cells and a decrease in their cytotoxicity. Rosuvastatin also led to an inhibition in apoptosis and ERS in H/R‑induced PC12 cells. After administration of the ERS response activator thapsigargin (TG), TG was found to reverse the protective effect of rosuvastatin on injury of H/R‑induced PC12 cells. Taken together, these findings have shown that rosuvastatin is able to protect PC12 cells from H/R‑induced injury via inhibiting ERS‑induced apoptosis, providing a strong theoretical basis for the use of rosuvastatin in the clinical treatment of CIRI.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Wang M, Wang J, Liu Z, Guo X, Wang N, Jia N, Zhang Y and Yuan J: Effects of intermedin on autophagy in cerebral ischemia/reperfusion injury. Neuropeptides. 68:15–21. 2018.PubMed/NCBI View Article : Google Scholar

2 

Deng Y, Zou W, Chen G, Shangguan S, Zhou F, Jiang W and Li X: Comparative studies on the effects of different doses of atorvastatin combined with aspirin on inflammatory cytokines and carotid plaques in patients with ischemic cerebrovascular disease. Int J Neurosci. 129:1133–1138. 2019.PubMed/NCBI View Article : Google Scholar

3 

Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW, Li CY and Li CJ: Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem. 46:1650–1667. 2018.PubMed/NCBI View Article : Google Scholar

4 

Sun MS, Jin H, Sun X, Huang S, Zhang FL, Guo ZN and Yang Y: Free radical damage in ischemia-reperfusion injury: An obstacle in acute ischemic stroke after revascularization therapy. Oxid Med Cell Longev. 2018(3804979)2018.PubMed/NCBI View Article : Google Scholar

5 

Xu F, Ma R, Zhang G, Wang S, Yin J, Wang E, Xiong E, Zhang Q and Li Y: Estrogen and propofol combination therapy inhibits endoplasmic reticulum stress and remarkably attenuates cerebral ischemia-reperfusion injury and OGD injury in hippocampus. Biomed Pharmacother. 108:1596–1606. 2018.PubMed/NCBI View Article : Google Scholar

6 

Lin YW, Chen TY, Hung CY, Tai SH, Huang SY, Chang CC, Hung HY and Lee EJ: Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress. Int J Mol Med. 42:182–192. 2018.PubMed/NCBI View Article : Google Scholar

7 

Feng D, Wang B, Wang L, Abraham N, Tao K, Huang L, Shi W, Dong Y and Qu Y: Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalings. J Pineal Res. 62:2017.PubMed/NCBI View Article : Google Scholar

8 

Nakka VP, Gusain A and Raghubir R: Endoplasmic reticulum stress plays critical role in brain damage after cerebral ischemia/reperfusion in rats. Neurotox Res. 17:189–202. 2010.PubMed/NCBI View Article : Google Scholar

9 

Xin Q, Ji B, Cheng B, Wang C, Liu H, Chen X, Chen J and Bai B: Endoplasmic reticulum stress in cerebral ischemia. Neurochem Int. 68:18–27. 2014.PubMed/NCBI View Article : Google Scholar

10 

Ishige K, Osada N, Kosuge Y and Ito Y: Involvement of endoplasmic reticulum stress in neurodegeneration after transient global ischemia-reperfusion. Nihon Yakurigaku Zasshi. 142:9–12. 2013.PubMed/NCBI View Article : Google Scholar : (In Japanese).

11 

Gong L, Tang Y, An R, Lin M, Chen L and Du J: RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways. Cell Death Dis. 8(e3080)2017.PubMed/NCBI View Article : Google Scholar

12 

Feng SQ, Zong SY, Liu JX, Chen Y, Xu R, Yin X, Zhao R, Li Y and Luo TT: VEGF antagonism attenuates cerebral ischemia/reperfusion-induced injury via inhibiting endoplasmic reticulum stress-mediated apoptosis. Biol Pharm Bull. 42:692–702. 2019.PubMed/NCBI View Article : Google Scholar

13 

Gutiérrez-Vargas JA, Cespedes-Rubio A and Cardona-Gómez GP: Perspective of synaptic protection after post-infarction treatment with statins. J Transl Med. 13(118)2015.PubMed/NCBI View Article : Google Scholar

14 

Cortese F, Gesualdo M, Cortese A, Carbonara S, Devito F, Zito A, Ricci G, Scicchitano P and Ciccone MM: Rosuvastatin: Beyond the cholesterol-lowering effect. Pharmacol Res. 107:1–18. 2016.PubMed/NCBI View Article : Google Scholar

15 

Liu Y, Yang H, Jia G, Li L, Chen H, Bi J and Wang C: The synergistic neuroprotective effects of combined rosuvastatin and resveratrol pretreatment against cerebral ischemia/reperfusion injury. J Stroke Cerebrovasc Dis. 27:1697–1704. 2018.PubMed/NCBI View Article : Google Scholar

16 

Ma M, Uekawa K, Hasegawa Y, Nakagawa T, Katayama T, Sueta D, Toyama K, Kataoka K, Koibuchi N, Kuratsu J and Kim-Mitsuyama S: Pretreatment with rosuvastatin protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress and inflammation. Brain Res. 1519:87–94. 2013.PubMed/NCBI View Article : Google Scholar

17 

Engelhorn T, Doerfler A, Heusch G and Schulz R: Reduction of cerebral infarct size by the AT1-receptor blocker candesartan, the HMG-CoA reductase inhibitor rosuvastatin and their combination. An experimental study in rats. Neurosci Lett. 406:92–96. 2006.PubMed/NCBI View Article : Google Scholar

18 

Xu JZ, Chai YL and Zhang YL: Effect of rosuvastatin on high glucose-induced endoplasmic reticulum stress in human umbilical vein endothelial cells. Genet Mol Res. 15:2016.PubMed/NCBI View Article : Google Scholar

19 

Geng J, Xu H, Fu W, Yu X, Xu G, Cao H, Lin G and Sui D: Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE-/- mice by suppressing endoplasmic reticulum stress. Exp Ther Med. 20:550–560. 2020.PubMed/NCBI View Article : Google Scholar

20 

Chen H and Li X: LncRNA ROR is involved in cerebral hypoxia/reoxygenation-induced injury in PC12 cells via regulating miR-135a-5p/ROCK1/2. Am J Transl Res. 11:6145–6158. 2019.PubMed/NCBI

21 

Oakes SA and Papa FR: The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol. 10:173–194. 2015.PubMed/NCBI View Article : Google Scholar

22 

Zhang K and Kaufman RJ: The unfolded protein response: A stress signaling pathway critical for health and disease. Neurology. 66 (2 Suppl 1):S102–S109. 2006.PubMed/NCBI View Article : Google Scholar

23 

Han ZW, Chang YC, Zhou Y, Zhang H, Chen L, Zhang Y, Si JQ and Li L: GPER agonist G1 suppresses neuronal apoptosis mediated by endoplasmic reticulum stress after cerebral ischemia/reperfusion injury. Neural Regen Res. 14:1221–1229. 2019.PubMed/NCBI View Article : Google Scholar

24 

Zhong CJ, Chen MM, Lu M, Ding JH, Du RH and Hu G: Astrocyte-specific deletion of Kir6.1/K-ATP channel aggravates cerebral ischemia/reperfusion injury through endoplasmic reticulum stress in mice. Exp Neurol. 311:225–233. 2019.PubMed/NCBI View Article : Google Scholar

25 

Wang X, Chen J and Huang X: Rosuvastatin attenuates myocardial ischemia-reperfusion injury via upregulating miR-17-3p-mediated autophagy. Cell Reprogram. 21:323–330. 2019.PubMed/NCBI View Article : Google Scholar

26 

Vélez DE, Mestre-Cordero VE, Hermann R, Perego J, Harriet S, Fernandez-Pazos MLM, Mourglia J and Marina-Prendes MG: Rosuvastatin protects isolated hearts against ischemia-reperfusion injury: Role of Akt-GSK-3β, metabolic environment, and mitochondrial permeability transition pore. J Physiol Biochem. 76:85–98. 2020.PubMed/NCBI View Article : Google Scholar

27 

Griffin JM, Kho D, Graham ES, Nicholson LF and O'Carroll SJ: Statins inhibit fibrillary β-amyloid induced inflammation in a model of the human blood brain barrier. PLoS One. 11(e0157483)2016.PubMed/NCBI View Article : Google Scholar

28 

Rodriguez-Perea AL, Gutierrez-Vargas J, Cardona-Gómez GP, Guarin CJ, Rojas M and Hernández PA: Atorvastatin modulates regulatory T cells and attenuates cerebral damage in a model of transient middle cerebral artery occlusion in rats. J Neuroimmune Pharmacol. 12:152–162. 2017.PubMed/NCBI View Article : Google Scholar

29 

Sohn HM, Hwang JY, Ryu JH, Kim J, Park S, Park JW and Han SH: Simvastatin protects ischemic spinal cord injury from cell death and cytotoxicity through decreasing oxidative stress: In vitro primary cultured rat spinal cord model under oxygen and glucose deprivation-reoxygenation conditions. J Orthop Surg Res. 12(36)2017.PubMed/NCBI View Article : Google Scholar

30 

Saleh DO, Mansour DF and Mostafa RE: Rosuvastatin and simvastatin attenuate cisplatin-induced cardiotoxicity via disruption of endoplasmic reticulum stress-mediated apoptotic death in rats: Targeting ER-chaperone GRP78 and calpain-1 pathways. Toxicol Rep. 7:1178–1186. 2020.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Gao Y, Li L, Yu J and Zhang Z: Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis. Exp Ther Med 22: 1189, 2021.
APA
Gao, Y., Li, L., Yu, J., & Zhang, Z. (2021). Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis. Experimental and Therapeutic Medicine, 22, 1189. https://doi.org/10.3892/etm.2021.10623
MLA
Gao, Y., Li, L., Yu, J., Zhang, Z."Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis". Experimental and Therapeutic Medicine 22.4 (2021): 1189.
Chicago
Gao, Y., Li, L., Yu, J., Zhang, Z."Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1189. https://doi.org/10.3892/etm.2021.10623
Copy and paste a formatted citation
x
Spandidos Publications style
Gao Y, Li L, Yu J and Zhang Z: Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis. Exp Ther Med 22: 1189, 2021.
APA
Gao, Y., Li, L., Yu, J., & Zhang, Z. (2021). Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis. Experimental and Therapeutic Medicine, 22, 1189. https://doi.org/10.3892/etm.2021.10623
MLA
Gao, Y., Li, L., Yu, J., Zhang, Z."Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis". Experimental and Therapeutic Medicine 22.4 (2021): 1189.
Chicago
Gao, Y., Li, L., Yu, J., Zhang, Z."Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1189. https://doi.org/10.3892/etm.2021.10623
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team