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
November-2018 Volume 16 Issue 5

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
November-2018 Volume 16 Issue 5

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

Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells

  • Authors:
    • Xiao Wei
    • Dan Zhu
    • Chenchen Feng
    • Guofang Chen
    • Xiaodong Mao
    • Qifeng Wang
    • Jie Wang
    • Chao Liu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China, Department of Endocrinology, Jiangdu People's Hospital of Yangzhou, Yangzhou, Jiangsu 225200, P.R. China, Central Laboratory, Jiangsu Province Blood Center, Nanjing, Jiangsu 210042, P.R. China
    Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3959-3964
    |
    Published online on: September 7, 2018
       https://doi.org/10.3892/etm.2018.6706
  • 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

Cyclosporin A (CsA) is widely used as an immunosuppressor in the context of organ transplantation or autoimmune disorders. Recent studies have revealed the detrimental effects of CsA on insulin resistance and pancreatic β cell failure; however, the molecular mechanisms are unknown. The present study sought to confirm the associations between CsA and β cell failure, and to investigate the roles of proinsulin folding and endoplasmic reticulum (ER) stress in CsA‑induced β cell failure. The viability of MIN6 cells treated with CsA was evaluated with MTT assay. Expression levels of insulin, peptidyl‑prolyl cis‑trans isomerase B (PPIB), cleaved caspase‑3, phospho‑protein kinase R (PKR)‑like endoplasmic reticulum kinase (p‑PERK), PKR‑like endoplasmic reticulum kinase (PERK), binding immunoglobulin protein (BIP), and C/EBP homologous protein (CHOP) were detected via reducing western blot assay. Non‑reducing western blot analysis was performed to examine the expression of misfolded proinsulin peptides. The proliferation of MIN6 cells was not inhibited by CsA at concentrations <1 µmol/l. CsA treatment resulted in the decreased expression of insulin and PPIB; however, it also increased the phosphorylation of PERK, and upregulated the expression of PERK, BIP, CHOP and cleaved caspase‑3. The results indicated that CsA could induce pancreatic β cell dysfunction and the potential mechanism underlying this phenomenon may be PPIB‑associated proinsulin misfolding, which in turn induces ER stress in β cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Shivaswamy V, Boerner B and Larsen J: Post-transplant diabetes mellitus: Causes, treatment, and impact on outcomes. Endocr Rev. 37:37–61. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Wang X, Hu YC, Zhang RY, Jin DX, Jiang Y, Zhang HN and Cong HL: Effect of cyclosporin A intervention on the immunological mechanisms of coronary heart disease and restenosis. Exp Ther Med. 12:3242–3248. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Bhat M, Pasini E, Copeland J, Angeli M, Husain S, Kumar D, Renner E, Teterina A, Allard J, Guttman DS and Humar A: Impact of immunosuppression on the metagenomic composition of the intestinal microbiome: A systems biology approach to post-transplant diabetes. Sci Rep. 7:102772017. View Article : Google Scholar : PubMed/NCBI

4 

Azzi JR, Sayegh MH and Mallat SG: Calcineurin inhibitors: 40 years later, can't live without. J Immunol. 191:5785–5791. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Langsford D and Dwyer K: Dysglycemia after renal transplantation: Definition, pathogenesis, outcomes, and implications for management. World J Diabetes. 6:1132–1151. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Montero N and Pascual J: Immunosuppression and Post-transplant Hyperglycemia. Curr Diabetes Rev. 11:144–154. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Palepu S and Prasad GV: New-onset diabetes mellitus after kidney transplantation: Current status and future directions. World J Diabetes. 6:445–455. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Øzbay LA, Smidt K, Mortensen DM, Carstens J, Jørgensen KA and Rungby J: Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS-1E beta-cells. Br J Pharmacol. 162:136–146. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Pereira MJ, Palming J, Rizell M, Aureliano M, Carvalho E, Svensson MK and Eriksson JW: Cyclosporine A and tacrolimus reduce the amount of GLUT4 at the cell surface in human adipocytes: Increased endocytosis as a potential mechanism for the diabetogenic effects of immunosuppressive agents. J Clin Endocrinol Metab. 99:E1885–E1894. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Bai Y, Wei Y, Wu L, Wei J, Wang X and Bai Y: C/EBP β mediates endoplasmic reticulum stress regulated inflammatory response and extracellular matrix degradation in LPS-stimulated human periodontal ligament cells. Int J Mol Sci. 17:3852016. View Article : Google Scholar : PubMed/NCBI

11 

Liu M, Wright J, Guo H, Xiong Y and Arvan P: Proinsulin entry and transit through the endoplasmic reticulum in pancreatic beta cells. Vitam Horm. 95:35–62. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Ozawa S, Katsuta H, Suzuki K, Takahashi K, Tanaka T, Sumitani Y, Nishida S, Yoshimoto K and Ishida H: Estimated proinsulin processing activity of prohormone convertase (PC) 1/3 rather than PC2 is decreased in pancreatic β-cells of type 2 diabetic patients. Endocr J. 61:607–614. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Zhang X, Yuan Q, Tang W, Gu J, Osei K and Wang J: Substrate-favored lysosomal and proteasomal pathways participate in the normal balance control of insulin precursor maturation and disposal in β-cells. PLoS One. 6:e276472011. View Article : Google Scholar : PubMed/NCBI

14 

Kim G, Kim JY and Choi HS: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 as a therapeutic target in hepatocellular carcinoma. Biol Pharm Bull. 38:975–979. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Ren LQ, Liu W, Li WB, Liu WJ and Sun L: Peptidylprolyl cis/trans isomerase activity and molecular evolution of vertebrate cyclophilin A. Yi Chuan. 38:736–745. 2016.PubMed/NCBI

16 

Humbert MV, Mendoza Almonacid HL, Jackson AC, Hung MC, Bielecka MK, Heckels JE and Christodoulides M: Vaccine potential of bacterial macrophage infectivity potentiator (MIP)-like peptidyl prolyl cis/trans isomerase (PPIase) proteins. Expert Rev Vaccines. 14:1633–1649. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Cho KI, Orry A, Park SE and Ferreira PA: Targeting the cyclophilin domain of Ran-binding protein 2 (Ranbp2) with novel small molecules to control the proteostasis of STAT3, hnRNPA2B1 and M-opsin. ACS Chem Neurosci. 6:1476–1485. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Ernst K, Langer S, Kaiser E, Osseforth C, Michaelis J, Popoff MR, Schwan C, Aktories K, Kahlert V, Malesevic M, et al: Cyclophilin-facilitated membrane translocation as pharmacological target to prevent intoxication of mammalian cells by binary clostridial actin ADP-ribosylated toxins. J Mol Biol. 427:1224–1238. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Tafazoli A: Cyclosporine use in hematopoietic stem cell transplantation: Pharmacokinetic approach. Immunotherapy. 7:811–836. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Wang Z and Zhang L: Treatment effect of cyclosporine A in patients with painful bladder syndrome/interstitial cystitis: A systematic review. Exp Ther Med. 12:445–450. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Wang J and Osei K: Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in β-cells. Biochem Biophys Res Commun. 411:150–155. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Wang J, Chen Y, Yuan Q, Tang W, Zhang X and Osei K: Control of precursor maturation and disposal is an early regulative mechanism in the normal insulin production of pancreatic β-cells. PLoS One. 6:e194462011. View Article : Google Scholar : PubMed/NCBI

23 

Yuan Q, Tang W, Zhang X, Hinson JA, Liu C, Osei K and Wang J: Proinsulin atypical maturation and disposal induces extensive defects in mouse Ins2+/Akita β-cells. PLoS One. 7:e350982012. View Article : Google Scholar : PubMed/NCBI

24 

Fu Z, Gilbert ER and Liu D: Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev. 9:25–53. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Chan JY, Luzuriaga J, Maxwell EL, West PK, Bensellam M and Laybutt DR: The balance between adaptive and apoptotic unfolded protein responses regulates β-cell death under ER stress conditions through XBP1, CHOP and JNK. Mol Cell Endocrinol. 413:189–201. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Yu C, Cui S, Zong C, Gao W, Xu T, Gao P, Chen J, Qin D, Guan Q, Liu Y, et al: The orphan nuclear receptor NR4A1 protects pancreatic β-cells from endoplasmic reticulum (ER) stress-mediated apoptosis. J Biol Chem. 290:20687–20699. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Kwak HJ, Choi HE, Jang J, Park SK, Bae YA and Cheon HG: Bortezomib attenuates palmitic acid-induced ER stress, inflammation and insulin resistance in myotubes via AMPK dependent mechanism. Cell Signal. 28:788–797. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Oh YS, Lee YJ, Kang Y, Han J, Lim OK and Jun HS: Exendin-4 inhibits glucolipotoxic ER stress in pancreatic β cells via regulation of SREBP1c and C/EBPβ transcription factors. J Endocrinol. 216:343–352. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Cumaoglu A, Arıcıoglu A and Karasu C: Redox status related activation of endoplasmic reticulum stress and apoptosis caused by 4-hydroxynonenal exposure in INS-1 cells. Toxicol Mech Methods. 24:362–367. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Reid DW, Chen Q, Tay AS, Shenolikar S and Nicchitta CV: The unfolded protein response triggers selective mRNA release from the endoplasmic reticulum. Cell. 158:1362–1374. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wei X, Zhu D, Feng C, Chen G, Mao X, Wang Q, Wang J and Liu C: Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells. Exp Ther Med 16: 3959-3964, 2018.
APA
Wei, X., Zhu, D., Feng, C., Chen, G., Mao, X., Wang, Q. ... Liu, C. (2018). Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells. Experimental and Therapeutic Medicine, 16, 3959-3964. https://doi.org/10.3892/etm.2018.6706
MLA
Wei, X., Zhu, D., Feng, C., Chen, G., Mao, X., Wang, Q., Wang, J., Liu, C."Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells". Experimental and Therapeutic Medicine 16.5 (2018): 3959-3964.
Chicago
Wei, X., Zhu, D., Feng, C., Chen, G., Mao, X., Wang, Q., Wang, J., Liu, C."Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells". Experimental and Therapeutic Medicine 16, no. 5 (2018): 3959-3964. https://doi.org/10.3892/etm.2018.6706
Copy and paste a formatted citation
x
Spandidos Publications style
Wei X, Zhu D, Feng C, Chen G, Mao X, Wang Q, Wang J and Liu C: Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells. Exp Ther Med 16: 3959-3964, 2018.
APA
Wei, X., Zhu, D., Feng, C., Chen, G., Mao, X., Wang, Q. ... Liu, C. (2018). Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells. Experimental and Therapeutic Medicine, 16, 3959-3964. https://doi.org/10.3892/etm.2018.6706
MLA
Wei, X., Zhu, D., Feng, C., Chen, G., Mao, X., Wang, Q., Wang, J., Liu, C."Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells". Experimental and Therapeutic Medicine 16.5 (2018): 3959-3964.
Chicago
Wei, X., Zhu, D., Feng, C., Chen, G., Mao, X., Wang, Q., Wang, J., Liu, C."Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells". Experimental and Therapeutic Medicine 16, no. 5 (2018): 3959-3964. https://doi.org/10.3892/etm.2018.6706
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