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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
February-2016 Volume 13 Issue 2

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
February-2016 Volume 13 Issue 2

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

Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway

  • Authors:
    • Jianbin Zhong
    • Xie Li
    • Limei Wan
    • Zhibang Chen
    • Simin Zhong
    • Songhua Xiao
    • Zhengwen Yan
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Zeng Cheng People's Hospital and Boji Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 511300, P.R. China, Department of Neurology, Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 511300, P.R. China
  • Pages: 1427-1433
    |
    Published online on: December 4, 2015
       https://doi.org/10.3892/mmr.2015.4637
  • 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

NogoA is a myelin‑associated protein, which is important in the inhibition of axonal fiber growth and in regeneration following injury of the mammalian central nervous system. A previous study suggested that NogoA may be key in the process of Parkinson's disease (PD), which is the second most common chronic neurodegenerative disorder worldwide. The regulatory mechanism underlying the effect of NogoA on the process of PD remains to be fully elucidated. The present study aimed to investigate the effect and underlying mechanism of NogoA on cellular viability, apoptosis and autophagy induced by 1‑methyl‑4‑phenylpyridinium (MPP+) in PC12 cells, a commonly used in vitro PD model. PC12 cells were treated with 1 mM MPP+ for 24 h and the cells were harvested for western blotting. The results demonstrated that the protien expression levels of NogoA were increased in the PC12 cells treated with MPP+. Subsequently, NogoA small interfering RNA was synthesized and transfected into PC12 cells to silence the expression of NogoA. NogoA knockdown significantly reduced the MPP+‑induced decrease in cell viability and apoptosis, detected using a cell counting kit‑8 and flow cytometric analysis, respectively. Interference in the expression of NogoA increased the MPP+‑induced decrease in mitochondrial membrane potential, determined quantitatively by flow cytometry using JC-1 dye, and the protein levels of Beclin‑1. In addition, MPP+ treatment activated the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Knockdown of NogoA significantly inhibited the expression levels of mTOR and STAT3. Furthermore, overexpression of NogoA had similar neurotoxic effects on the PC12 cells as MPP+ treatment. Treatment with rapamycin, an inhibitor of the mTOR/STAT3 signaling pathway had a similar effect to that of NogoA knockdown in the MPP+‑treated PC12 cells. Taken together, the results from the present study demonstrated that NogoA may regulate MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway and provided an explanation regarding the regulatory mechanism of NogoA on the process of PD.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

de Lau LM, Koudstaal PJ, Hofman A and Breteler MM: Subjective complaints precede Parkinson disease: The rotterdam study. Arch Neurol. 63:362–365. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Schapira AH and Olanow CW: Neuroprotection in Parkinson disease: Mysteries, myths, and misconceptions. JAMA. 291:358–364. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Hirsch E, Graybiel AM and Agid YA: Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature. 334:345–348. 1988. View Article : Google Scholar : PubMed/NCBI

4 

Jellinger KA: The pathology of Parkinson's disease. Adv Neurol. 86:55–72. 2001.PubMed/NCBI

5 

Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN and Braak E: Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 24:197–211. 2003. View Article : Google Scholar

6 

Fahn S and Sulzer D: Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx. 1:139–154. 2004. View Article : Google Scholar

7 

Braak H, Ghebremedhin E, Rüb U, Bratzke H and Del Tredici K: Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 318:121–134. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Chaudhuri KR and Odin P: The challenge of non-motor symptoms in Parkinson's disease. Prog Brain Res. 184:325–341. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Hou RR, Chen JZ, Chen H, Kang XG, Li MG and Wang BR: Neuroprotective effects of (−)-epigallocatechin-3-gallate (EGCG) on paraquat-induced apoptosis in PC12 cells. Cell Biol Int. 32:22–30. 2008. View Article : Google Scholar

10 

Schwab ME: Functions of Nogo proteins and their receptors in the nervous system. Nat Rev Neurosci. 11:799–811. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Zagrebelsky M, Schweigreiter R, Bandtlow CE, Schwab ME and Korte M: Nogo-A stabilizes the architecture of hippocampal neurons. J Neurosci. 30:13220–13234. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Kempf A and Schwab ME: Nogo-A represses anatomical and synaptic plasticity in the central nervous system. Physiology (Bethesda). 28:151–163. 2013. View Article : Google Scholar

13 

Mironova YA and Giger RJ: Where no synapses go: Gatekeepers of circuit remodeling and synaptic strength. Trends Neurosci. 36:363–373. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Jitoku D, Hattori E, Iwayama Y, Yamada K, Toyota T, Kikuchi M, Maekawa M, Nishikawa T and Yoshikawa T: Association study of Nogo-related genes with schizophrenia in a Japanese case-control sample. Am J Med Genet B Neuropsychiatr Genet. 156B:581–592. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Krištofiková Z, Vrajová M, Sirová J, Valeš K, Petrásek T, Schönig K, Tews B, Schwab M, Bartsch D, Stuchlík A and Rípová D: N-Methyl-d-Aspartate receptor - Nitric oxide synthase pathway in the cortex of Nogo-A-Deficient rats in relation to brain laterality and schizophrenia. Front Behav Neurosci. 7:902013. View Article : Google Scholar

16 

Delekate A, Zagrebelsky M, Kramer S, Schwab ME and Korte M: NogoA restricts synaptic plasticity in the adult hippocampus on a fast time scale. Proc Natl Acad Sci USA. 108:2569–2574. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Zemmar A, Weinmann O, Kellner Y, Yu X, Vicente R, Gullo M, Kasper H, Lussi K, Ristic Z, Luft AR, et al: Neutralization of Nogo-A enhances synaptic plasticity in the rodent motor cortex and improves motor learning in vivo. J Neurosci. 34:8685–8698. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Wälchli T, Pernet V, Weinmann O, Shiu JY, Guzik-Kornacka A, Decrey G, Yüksel D, Schneider H, Vogel J, Ingber DE, et al: Nogo-A is a negative regulator of CNS angiogenesis. Proc Natl Acad Sci USA. 110:E1943–E1952. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Willi R, Weinmann O, Winter C, Klein J, Sohr R, Schnell L, Yee BK, Feldon J and Schwab ME: Constitutive genetic deletion of the growth regulator Nogo-A induces schizophrenia-related endophenotypes. J Neurosci. 30:556–567. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Tews B, Schönig K, Arzt ME, Clementi S, Rioult-Pedotti MS, Zemmar A, Berger SM, Schneider M, Enkel T, Weinmann O, et al: Synthetic microRNA-mediated downregulation of Nogo-A in transgenic rats reveals its role as regulator of synaptic plasticity and cognitive function. Proc Natl Acad Sci USA. 110:6583–6588. 2013. View Article : Google Scholar : PubMed/NCBI

21 

GrandPré T, Li S and Strittmatter SM: Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature. 417:547–551. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Wang H, Shen J, Xiong N, Zhao H and Chen Y: Protein kinase B is involved in Nogo-66 inhibiting neurite outgrowth in PC12 cells. Neuroreport. 22:733–738. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Yan J, Zhou X, Guo JJ, Mao L, Wang YJ, Sun J, Sun LX, Zhang LY, Zhou XF and Liao H: Nogo-66 inhibits adhesion and migration of microglia via GTPase Rho pathway in vitro. J Neurochem. 120:721–731. 2012. View Article : Google Scholar

24 

Cossarizza A, Baccarani-Contri M, Kalashnikova G and Franceschi C: A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-benzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun. 197:40–45. 1993. View Article : Google Scholar : PubMed/NCBI

25 

Akbik F, Cafferty WB and Strittmatter SM: Myelin associated inhibitors: A link between injury-induced and experience-dependent plasticity. Exp Neurol. 235:43–52. 2012. View Article : Google Scholar

26 

Pernet V and Schwab ME: The role of Nogo-A in axonal plasticity, regrowth and repair. Cell Tissue Res. 349:97–104. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Rolando C, Parolisi R, Boda E, Schwab ME, Rossi F and Buffo A: Distinct roles of Nogo-a and Nogo receptor 1 in the homeostatic regulation of adult neural stem cell function and neuroblast migration. J Neurosci. 32:17788–17799. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Willi R and Schwab ME: Nogo and Nogo receptor: Relevance to schizophrenia? Neurobiol Dis. 54:150–157. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Deng Q and Yang X: Protective effects of Gynostemma pentaphyllum polysaccharides on PC12 cells impaired by MPP(+). Int J Biol Macromol. 69:171–175. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Cheng B, Guo Y, Li C, Ji B, Pan Y, Chen J and Bai B: Edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating heme oxygenase-1 expression. J Neurol Sci. 343:115–119. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Swiech L, Perycz M, Malik A and Jaworski J: Role of mTOR in physiology and pathology of the nervous system. Biochim Biophys Acta. 1784:116–132. 2008. View Article : Google Scholar

32 

Jiang LB, Cao L, Yin XF, Yasen M, Yishake M, Dong J and Li XL: Activation of autophagy via Ca(2+) dependent AMPK/mTOR pathway in rat notochordal cells is a cellular adaptation under hyperosmotic stress. Cell Cycle. 14:867–879. 2015. View Article : Google Scholar

33 

Kumar S, Guru SK, Pathania AS, Manda S, Kumar A, Bharate SB, Vishwakarma RA, Malik F and Bhushan S: Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells. J Cell Biochem. 116:985–997. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Mukhopadhyay S, Panda PK, Sinha N, Das DN and Bhutia SK: Autophagy and apoptosis: Where do they meet? Apoptosis. 19:555–566. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhong J, Li X, Wan L, Chen Z, Zhong S, Xiao S and Yan Z: Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway. Mol Med Rep 13: 1427-1433, 2016.
APA
Zhong, J., Li, X., Wan, L., Chen, Z., Zhong, S., Xiao, S., & Yan, Z. (2016). Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway. Molecular Medicine Reports, 13, 1427-1433. https://doi.org/10.3892/mmr.2015.4637
MLA
Zhong, J., Li, X., Wan, L., Chen, Z., Zhong, S., Xiao, S., Yan, Z."Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway". Molecular Medicine Reports 13.2 (2016): 1427-1433.
Chicago
Zhong, J., Li, X., Wan, L., Chen, Z., Zhong, S., Xiao, S., Yan, Z."Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway". Molecular Medicine Reports 13, no. 2 (2016): 1427-1433. https://doi.org/10.3892/mmr.2015.4637
Copy and paste a formatted citation
x
Spandidos Publications style
Zhong J, Li X, Wan L, Chen Z, Zhong S, Xiao S and Yan Z: Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway. Mol Med Rep 13: 1427-1433, 2016.
APA
Zhong, J., Li, X., Wan, L., Chen, Z., Zhong, S., Xiao, S., & Yan, Z. (2016). Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway. Molecular Medicine Reports, 13, 1427-1433. https://doi.org/10.3892/mmr.2015.4637
MLA
Zhong, J., Li, X., Wan, L., Chen, Z., Zhong, S., Xiao, S., Yan, Z."Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway". Molecular Medicine Reports 13.2 (2016): 1427-1433.
Chicago
Zhong, J., Li, X., Wan, L., Chen, Z., Zhong, S., Xiao, S., Yan, Z."Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway". Molecular Medicine Reports 13, no. 2 (2016): 1427-1433. https://doi.org/10.3892/mmr.2015.4637
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