Suppression of c-jun influences nNOS expression in differentiated PC12 cells

Cheng,Xiao; Liu,Shu; Wang,Ya-Qiong; Li,Ying-Qin; Fu,Rao; Tang,Ying; Zheng,Wen-Hua; Zhou,Li-Hua

doi:10.3892/mmr.2012.987

October 2012 Volume 6 Issue 4

Full Size Image

Journals

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 is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

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

Oncology Reports

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

Experimental and Therapeutic Medicine

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

Oncology Letters

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

Biomedical Reports

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

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

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

International Journal of Functional Nutrition

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

International Journal of Epigenetics

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

Medicine International

An International Open Access Journal Devoted to General Medicine.

October 2012 Volume 6 Issue 4

Full Size Image

Article

Suppression of c-jun influences nNOS expression in differentiated PC12 cells

Authors:
- Xiao Cheng
- Shu Liu
- Ya-Qiong Wang
- Ying-Qin Li
- Rao Fu
- Ying Tang
- Wen-Hua Zheng
- Li-Hua Zhou
View Affiliations / Copyright

Affiliations: Department of Anatomy, Zhong Shan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, P.R. China , State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou 510080, P.R. China
Pages: 750-754
|
Published online on: July 12, 2012

https://doi.org/10.3892/mmr.2012.987
Expand metrics +

Abstract

In various animal models of central neuronal diseases, both c-jun and nNOS genes are expressed inside injured neurons; however, the mechanism of these two genes in neuronal diseases remains uncertain. Our previous studies have shown that c-jun expression always occurs prior to expression of nNOS in motoneuron injuries. We aimed to determine whether there is a correlation between c-jun and nNOS, and whether the crosstalk between these two genes regulated the pathological progression of injury-induced neuronal degeneration. In the present study, we used the neuron-like differentiated PC12 cells, which express c-jun and nNOS, to examine whether c-jun is the upstream molecule modulating nNOS expression. The c-jun small interfering RNAs (c-jun siRNA) were transfected into PC12 cells and cells were treated for 72 h in vitro. Western blotting and immunofluorescence were used to check the protein levels and the expression of c-jun and nNOS in differentiated PC12 cells. The results from the immunofluorescence experiments showed that the c-jun and nNOS proteins were co-expressed in the differentiated PC12 cells. The results from the western blotting experiments revealed that the protein levels of c-jun were significantly decreased by c-jun siRNA. Moreover, the nNOS protein levels were also downregulated in differentiated PC12 cells following c-jun siRNA treatment. The present study found that siRNA used against c-jun not only knocked down c-jun, but also downregulated the nNOS protein expression in differentiated PC12 cells. These results indicate that there is a functional relationship between c-jun and nNOS in differentiated PC12 cells.

View Figures

View References

1	Karin M, Liu Z and Zandi E: AP-1 function and regulation. Curr Opin Cell Biol. 9:240–246. 1997. View Article : Google Scholar
2	Ham J, Babij C, Whitfield J, Pfarr CM, Lallemand D, Yaniv M and Rubin LL: A c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron. 14:927–939. 1995. View Article : Google Scholar : PubMed/NCBI
3	Hilberg F, Aguzzi A, Howells N and Wagner EF: c-jun is essential for normal mouse development and hepatogenesis. Nature. 365:179–181. 1993. View Article : Google Scholar : PubMed/NCBI
4	Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, Bar-Sagi D, Jones SN, Flavell RA and Davis RJ: Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science. 288:870–874. 2000. View Article : Google Scholar : PubMed/NCBI
5	Yun HY, Dawson VL and Dawson TM: Neurobiology of nitric oxide. Crit Rev Neurobiol. 10:291–316. 1996. View Article : Google Scholar
6	Phung YT, Bekker JM, Hallmark OG and Black SM: Both neuronal NO synthase and nitric oxide are required for PC12 cell differentiation: a cGMP independent pathway. Brain Res Mol Brain Res. 64:165–178. 1999. View Article : Google Scholar : PubMed/NCBI
7	Schonhoff CM, Bulseco DA, Brancho DM, Parada LF and Ross AH: 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
8	Pei DS, Song YJ, Yu HM, Hu WW, Du Y and Zhang GY: Exogenous nitric oxide negatively regulates c-Jun N-terminal kinase activation via inhibiting endogenous NO-induced S-nitrosylation during cerebral ischemia and reperfusion in rat hippocampus. J Neurochem. 106:1952–1963. 2008. View Article : Google Scholar
9	Lam PY and Cadenas E: Compromised proteasome degradation elevates neuronal nitric oxide synthase levels and induces apoptotic cell death. Arch Biochem Biophys. 478:181–186. 2008. View Article : Google Scholar : PubMed/NCBI
10	Treisman R: Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol. 8:205–215. 1996. View Article : Google Scholar : PubMed/NCBI
11	Li M, Wang L, Peng Y, Wang JC and Zhou LH: 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
12	Sheng M and Greenberg ME: The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron. 4:477–485. 1990. View Article : Google Scholar
13	Watson A, Eilers A, Lallemand D, Kyriakis J, Rubin LL and Ham J: 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
14	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 : PubMed/NCBI
15	Zeng XW, Li MW, Pan J, Ji TL, Yang B, Zhang B and Wang XQ: 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.PubMed/NCBI
16	Zhou LH, Han S, Xie YY, Wang LL and Yao ZB: 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	Wang LL, Zhao XC, Yan LF, Wang YQ, Cheng X, Fu R and Zhou LH: 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

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Suppression of c-jun influences nNOS expression in differentiated PC12 cells

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Related Articles