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
October 2014 Volume 10 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 2014 Volume 10 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

Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells

  • Authors:
    • Xiao Cheng
    • Haoxuan Luo
    • Zijun Hou
    • Yan Huang
    • Jingbo Sun
    • Lihua Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Encephalopathy, Encephalopathy Center, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China, Department of Anatomy, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China
  • Pages: 1881-1886
    |
    Published online on: July 23, 2014
       https://doi.org/10.3892/mmr.2014.2415
  • 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 high expression of c‑jun and neuronal nitric oxide synthase (nNOS) generally occurs in neurons following the generation of various animal models of central neuronal diseases. However, the mechanism between them in neuronal disease remains to be elucidated. Our previous studies demonstrated that the expression of c‑jun always occurs prior to expression of nNOS in motoneuron injuries and suppression of c‑jun expression by c‑jun siRNA decreased nNOS expression in differentiated PC12 cells. The present study aimed to examine whether there was an association of up and downstream regulation or crosstalk between c‑jun and nNOS in neurons. Using a culture of differentiated PC12 cells in vitro, the expression of nNOS and c‑jun in cells was investigated by immunofluorescence. The nNOS inhibitor 7‑nitroindazole (7‑NI) was used in differentiated PC12 cells to downregulate the expression of nNOS. The optimal concentration of 7‑NI on the viability and survival of cultured differentiated PC12 cells was selected using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium assay and the effects of 7‑NI on the activity of constitutive nitric oxide synthase (cNOS) in differentiated PC12 cells were determined using a NOS Activity Detection kit. The effects of 7‑NI on the gene expression of nNOS and c‑jun were detected by western blot analysis. The results from the immunofluorescence demonstrated that the c‑jun and nNOS protein were constantly expressed in PC12 cells. The cell viability of differentiated PC12 cells were significantly inhibited by treatment with 200 and 400 µmol/l 7‑NI, and the expression levels of the nNOS protein were significantly inhibited by treatment with 200 µmol/l 7‑NI. However, 7‑NI had no significant effect on the protein expression level of c‑jun and the total activities of cNOS. Based on our previous studies, which revealed that the nNOS gene was a downstream signaling molecule of the JNK/c‑jun signaling pathway in cultured neurons, the expression of nNOS downstream was able to be regulated by c‑jun which was the upstream molecule. Therefore, these results indicated that the association between them involved up and downregulation instead of crosstalk.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Wu W, Li L, Yick LW, et al: GDNF and BDNF alter the expression of neuronal NOS, c-Jun, and p75 and prevent motoneuron death following spinal root avulsion in adult rats. J Neurotrauma. 20:603–612. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Ozdemir M, Attar A and Kuzu L: Regenerative treatment in spinal cord injury. Curr Stem Cell Res Ther. 7:364–369. 2012. View Article : Google Scholar

3 

Förstermann U and Sessa WC: Nitric oxide synthases: regulation and function. Eur Heart J. 33:829–837. 2012.PubMed/NCBI

4 

Brown GC: Nitric oxide and neuronal death. Nitric Oxide. 23:153–165. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Umar S and van der Laarse A: Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 333:191–201. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Schonhoff CM and Bulseco DA: The Ras-ERK pathway is required for the induction of neuronal nitric oxide synthase in differentiating PC12 cells. J Neurochem. 78:631–639. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Raivich G: Transcribing the path to neurological recovery - from early signals through transcription factors to downstream effectors of successful regeneration. Ann Anat. 193:248–258. 2011. View Article : Google Scholar

8 

Kenney AM and Kocsis JD: Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia in vivo. J Neurosci. 18:1318–1328. 1998.PubMed/NCBI

9 

Mruthyunjaya S, Rumma M, Ravibhushan G, et al: c-Jun/AP-1 transcription factor regulates laminin-1-induced neurite outgrowth in human bone marrow mesenchymal stem cells: role of multiple signaling pathways. FEBS Lett. 585:1915–1922. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Ferrer I, Barrón S, Rodríquez-Farré E, et al: Ionizing radiation-induced apoptosis is associated with c-Jun expression and c-Jun/AP-1 activation in the developing cerebellum of the rat. Neurosci Lett. 202:105–108. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Fonseca MB, Nunes AF and Rodrigues CM: c-Jun regulates the stability of anti-apoptotic deltaNp63 in amyloid-beta-induced apoptosis. J Alzheimers Dis. 28:685–694. 2012.PubMed/NCBI

12 

Maritz MF, van der Watt PJ, Holderness N, et al: Inhibition of AP-1 suppresses cervical cancer cell proliferation and is associated with p21 expression. Biol Chem. 392:439–448. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Raivich G: c-Jun expression, activation and function in neural cell death, inflammation and repair. J Neurochem. 107:898–906. 2008.PubMed/NCBI

14 

Dragunow M, Xu R, Walton M, et al: c-Jun promotes neurite outgrowth and survival in PC12 cells. Brain Res Mol Brain Res. 83:20–33. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Wang LL, Zhao XC, Yan LF, et al: C-jun phosphorylation contributes to down regulation of neuronal nitric oxide synthase protein and motoneurons death in injured spinal cords following root-avulsion of the brachial plexus. Neuroscience. 189:397–407. 2011. View Article : Google Scholar

16 

Zhou LH, Han S, Xie YY, et al: Differences in c-jun and nNOS expression levels in motoneurons following different kinds of axonal injury in adult rats. Brain Cell Biol. 36:213–227. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Zhou L and Wu W: Antisense oligos to neuronal nitric oxide synthase aggravate motoneuron death induced by spinal root avulsion in adult rat. Exp Neurol. 197:84–92. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Cheng X, Liu S, Wang YQ, et al: Suppression of c-jun influences nNOS expression in differentiated PC12 cells. Mol Med Rep. 6:750–754. 2012.PubMed/NCBI

19 

Cheng X, Fu R, Gao M, et al: Intrathecal application of short interfering RNA knocks down c-jun expression and augments spinal motoneuron death after root avulsion in adult rats. Neuroscience. 241:268–279. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Li M, Wang L, Peng Y, et al: Knockdown of the neuronal nitric oxide synthase gene retard the development of the cerebellar granule neurons in vitro. Dev Dyn. 239:474–481. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Cheng X, Liu FL, Zhang J, et al: EGb761 protects motoneurons against avulsion-induced oxidative stress in rats. J Brachial Plex Peripher Nerve Inj. 5:122010. View Article : Google Scholar : PubMed/NCBI

22 

Li R, Wang WQ, Zhang H, et al: Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity. Am J Physiol Endocrinol Metab. 293:1703–1708. 2007. View Article : Google Scholar

23 

Palmada M, Kanwal S, Rutkoski NJ, et al: c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. J Cell Biol. 158:453–461. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Ham J, Babij C, Whitfeld J, et al: A c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron. 14:927–939. 1995. View Article : Google Scholar : PubMed/NCBI

25 

Watson A, Eilers A, Lallemand D, et al: Phosphorylation of c-Jun is necessary for apoptosis induced by survival signal withdrawal in cerebellar granule neurons. J Neurosci. 18:751–762. 1998.PubMed/NCBI

26 

Wang X, Tay SS and Ng YK: C-fos and c-jun expressions in nitric oxide synthase immunoreactive neurons in the lateral geniculate nucleus of experimental glaucomatous rats. Exp Brain Res. 144:365–372. 2002. View Article : Google Scholar

27 

Zeng XW, Li MW, Pan J, et al: Activation of c-Jun N-terminal kinase 1/2 regulated by nitric oxide is associated with neuronal survival in hippocampal neurons in a rat model of ischemia. Chin Med J (Engl). 124:3367–3372. 2011.

28 

Lam PY and Cadenas E: Compromised proteasome degradation elevates neuronal nitric oxide synthase levels and induced apoptotic cell death. Arch Biochem Biophys. 478:181–186. 2008. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cheng X, Luo H, Hou Z, Huang Y, Sun J and Zhou L: Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells. Mol Med Rep 10: 1881-1886, 2014.
APA
Cheng, X., Luo, H., Hou, Z., Huang, Y., Sun, J., & Zhou, L. (2014). Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells. Molecular Medicine Reports, 10, 1881-1886. https://doi.org/10.3892/mmr.2014.2415
MLA
Cheng, X., Luo, H., Hou, Z., Huang, Y., Sun, J., Zhou, L."Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells". Molecular Medicine Reports 10.4 (2014): 1881-1886.
Chicago
Cheng, X., Luo, H., Hou, Z., Huang, Y., Sun, J., Zhou, L."Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells". Molecular Medicine Reports 10, no. 4 (2014): 1881-1886. https://doi.org/10.3892/mmr.2014.2415
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng X, Luo H, Hou Z, Huang Y, Sun J and Zhou L: Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells. Mol Med Rep 10: 1881-1886, 2014.
APA
Cheng, X., Luo, H., Hou, Z., Huang, Y., Sun, J., & Zhou, L. (2014). Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells. Molecular Medicine Reports, 10, 1881-1886. https://doi.org/10.3892/mmr.2014.2415
MLA
Cheng, X., Luo, H., Hou, Z., Huang, Y., Sun, J., Zhou, L."Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells". Molecular Medicine Reports 10.4 (2014): 1881-1886.
Chicago
Cheng, X., Luo, H., Hou, Z., Huang, Y., Sun, J., Zhou, L."Neuronal nitric oxide synthase, as a downstream signaling molecule of c‑jun, regulates the survival of differentiated PC12 cells". Molecular Medicine Reports 10, no. 4 (2014): 1881-1886. https://doi.org/10.3892/mmr.2014.2415
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