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-2015 Volume 11 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-2015 Volume 11 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

Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema

  • Authors:
    • Gang Li
    • Xiaozhi Liu
    • Zhenlin Liu
    • Zhiguo Su
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Tianjin 5th Center Hospital, Tianjin 300450, P.R. China
  • Pages: 1188-1194
    |
    Published online on: November 5, 2014
       https://doi.org/10.3892/mmr.2014.2867
  • 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

Connexin 43 (Cx43) and aquaporin-4 (AQP4) have important roles in the formation of glioma-induced brain edema; however, the association between these two factors in the development of edema has remained to be elucidated. In the present study, immunofluorescence and western blot analysis revealed that in a rat model of intracranial C6 glioma, Cx43 expression levels were low to undetectable and AQP4 expression levels were low in glioma cells. Significantly higher Cx43 and AQP4 levels were detected in the tissue surrounding the glioma. To further investigate the potential interaction between Cx43 and AQP4, normal glial cells and C6 glioma cells were cultured in hypotonic medium. Reverse transcription quantitative polymerase chain reaction indicated that AQP4 and Cx43 mRNA expression levels increased as a function of time in normal glial cells and C6 glioma cells in a hypotonic environment. However, the increase observed in normal glial cells was significantly lower than that observed in C6 glioma cells. Furthermore, AQP4 expression levels changed prior to alterations in Cx43 expression. Following AQP4 silencing in C6 cells, the increase in Cx43 expression was significantly attenuated (P<0.05). In normal cells, Cx43 silencing did not influence AQP4 expression (P>0.05). Therefore, it was hypothesized that AQP4 and Cx43 had two distinct mechanisms underlying brain edema formation within and surrounding the glioma. Cx43 may be a downstream effector of AQP4. The elucidation of this pathway may aid in the development of drugs targeting the interaction between AQP4 and Cx43, providing novel therapeutic possibilities for glioma-induced brain edema.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Bonavia R, Inda MM, Cavenee WK and Furnari FB: Heterogeneity maintenance in glioblastoma: a social network. Cancer Res. 71:4055–4060. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Raizer JJ, Grimm S, Chamberlain MC, et al: A phase 2 trial of single-agent bevacizumab given in an every-3-week schedule for patients with recurrent high-grade gliomas. Cancer. 116:5297–5305. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Ivliev AE, ‘t Hoen PA and Sergeeva MG: Coexpression network analysis identifies transcriptional modules related to proastrocytic differentiation and sprouty signaling in glioma. Cancer Res. 70:10060–10070. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Gerstner ER, Chen PJ, Wen PY, Jain RK, Batchelor TT and Sorensen G: Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib. Neuro Oncol. 12:466–472. 2010.PubMed/NCBI

5 

Bleeker FE, Molenaar RJ and Leenstra S: Recent advances in the molecular understanding of glioblastoma. J Neurooncol. 108:11–27. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Masica DL and Karchin R: Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival. Cancer Res. 71:4550–4561. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Tabunoki H, Saito N, Suwanborirux K, Charupant K and Satoh J: Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids. Cancer Cell Int. 12:142012. View Article : Google Scholar : PubMed/NCBI

8 

Yoo AS, Sun AX, Li L, et al: MicroRNA-mediated conversion of human fibroblasts to neurons. Nature. 476:228–231. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Huang PH, Miraldi ER, Xu AM, et al: Phosphotyrosine signaling analysis of site-specific mutations on EGFRvIII identifies determinants governing glioblastoma cell growth. Mol Biosyst. 6:1227–1237. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Solan JL and Lampe PD: Connexin43 phosphorylation: structural changes and biological effects. Biochem J. 419:261–272. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Huang Q, Liu XZ, Kang CS, Wang GX, Zhong Y and Pu PY: The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cells. Cancer Gene Ther. 17:192–202. 2010. View Article : Google Scholar

12 

Li W and Graeber MB: The molecular profile of microglia under the influence of glioma. Neuro Oncol. 14:958–978. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Ribot EJ, Miraux S, Konsman JP, et al: In vivo MR tracking of therapeutic microglia to a human glioma model. NMR Biomed. 24:1361–1368. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Salvati M, D’Elia A, Formichella AI and Frati A: Insights into pharmacotherapy of malignant glioma in adults. Expert Opin Pharmacother. 10:2279–2290. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Xiong Z and Ohlfest JR: Topical imiquimod has therapeutic and immunomodulatory effects against intracranial tumors. J Immunother. 34:264–269. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Brisset AC, Isakson BE and Kwak BR: Connexins in Vascular Physiology and Pathology. Antioxid Redox Signal. 11:267–282. 2009. View Article : Google Scholar

17 

Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG and Batchelor TT: Angiogenesis in brain tumours. Nat Rev Neurosci. 8:610–622. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Papadopoulos MC, Saadoun S, Davies DC and Bell BA: Emerging molecular mechanisms of brain tumour oedema. Br J Neurosurg. 15:101–108. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Pavlisa G, Rados M, Pavlisa G, Pavic L, Potocki K and Mayer D: The differences of water diffusion between brain tissue infiltrated by tumor and peritumoral vasogenic edema. Clin Imaging. 33:96–101. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Uchida S, Sasaki S, Fushimi K and Marumo F: Isolation of human aquaporin-CD gene. J Biol Chem. 269:23451–23455. 1994.PubMed/NCBI

21 

Mou KJ, Mao Q, Chen MN, et al: AQP4 expression in the brains of patients with glioblastoma and its association with brain edema. Sichuan Da Xue Xue Bao Yi Xue Ban. 40:651–654. 2009.(In Chinese). PubMed/NCBI

22 

Nico B, Mangieri D, Tamma R, et al: Aquaporin-4 contributes to the resolution of peritumoural brain oedema in human glioblastoma multiforme after combined chemotherapy and radiotherapy. Eur J Cancer. 45:3315–3325. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Warth A, Mittelbronn M, Hülper P, Erdlenbruch B and Wolburg H: Expression of the water channel protein aquaporin-9 in malignant brain tumors. Appl Immunohistochem Mol Morphol. 15:193–198. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Nicchia GP, Srinivas M, Li W, Brosnan CF, Frigeri A and Spray DC: New possible roles for aquaporin-4 in astrocytes: cell cytoskeleton and functional relationship with connexin43. FASEB J. 19:1674–1676. 2005.PubMed/NCBI

25 

Li YH and Sun SQ: Effect of hypotonic medium on expression of aquaporin-4 in astrocytes. Zhonghua Yi Xue Za Zhi. 84:496–501. 2004.(In Chinese). PubMed/NCBI

26 

Arima H, Yamamoto N, Sobue K, et al: Hyperosmolar mannitol simulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem. 278:44525–44534. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Yang B, Zador Z and Verkman AS: Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem. 283:15280–15286. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Figueroa XF and Duling BR: Gap junctions in the control of vascular function. Antioxid Redox Signal. 11:251–266. 2009. View Article : Google Scholar

29 

Criscuolo GR: The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor. Yale J Biol Med. 66:277–314. 1993.PubMed/NCBI

30 

Bradford MM: Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI

31 

Simard JM, Kent TA, Chen M, Tarasov KV and Gerzanich V: Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol. 6:258–268. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Walcott BP, Kahle KT and Simard JM: Novel Treatment Targets for Cerebral Edema. Neurotherapeutics. 9:65–72. 2012. View Article : Google Scholar :

33 

Cottin S, Ghani K and Caruso M: Bystander effect in glioblastoma cells with a predominant cytoplasmic localization of connexin43. Cancer Gene Ther. 15:823–831. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Mennecier G, Derangeon M, Coronas V, Hervé JC and Mesnil M: Aberrant expression and localization of connexin43 and connexin30 in a rat glioma cell line. Mol Carcinog. 47:391–401. 2008. View Article : Google Scholar

35 

Pu P, Xia Z, Yu S and Huang Q: Altered expression of Cx43 in astrocytic tumors. Clin Neurol Neurosurg. 107:49–54. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Masato Y: Regulation, structure and function of brain aquaporin. Rinsho Shinkeigaku. 49:786–788. 2009.(In Japanese). View Article : Google Scholar : PubMed/NCBI

37 

Zhu SM and Pan CF: Effect of propofol upon ammonia-induced neocortical astrocyte swelling and aquaporin-4 expression. Zhonghua Yi Xue Za Zhi. 89:2077–2080. 2009.(In Chinese). PubMed/NCBI

38 

Chodobski A, Zink BJ and Szmydynger-Chodobska J: Blood-brain barrier pathophysiology in traumatic brain injury. Transl Stroke Res. 2:492–516. 2011. View Article : Google Scholar

39 

Ampawong S, Chaisri U, Viriyavejakul P, Nontprasert A, Grau GE and Pongponratn E: Electron microscopic features of brain edema in rodent cerebral malaria in relation to glial fibrillary acidic protein expression. Int J Clin Exp Pathol. 7:2056–2067. 2014.PubMed/NCBI

40 

Bailey DM, Bärtsch P, Knauth M and Baumgartner RW: Emerging concepts in acute mountain sickness and high-altitude cerebral edema: from the molecular to the morphological. Cell Mol Life Sci. 66:3583–3594. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Zador Z, Bloch O, Yao X and Manley GT: Aquaporins: role in cerebral edema and brain water balance. Prog Brain Res. 161:185–194. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li G, Liu X, Liu Z and Su Z: Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema. Mol Med Rep 11: 1188-1194, 2015.
APA
Li, G., Liu, X., Liu, Z., & Su, Z. (2015). Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema. Molecular Medicine Reports, 11, 1188-1194. https://doi.org/10.3892/mmr.2014.2867
MLA
Li, G., Liu, X., Liu, Z., Su, Z."Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema". Molecular Medicine Reports 11.2 (2015): 1188-1194.
Chicago
Li, G., Liu, X., Liu, Z., Su, Z."Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema". Molecular Medicine Reports 11, no. 2 (2015): 1188-1194. https://doi.org/10.3892/mmr.2014.2867
Copy and paste a formatted citation
x
Spandidos Publications style
Li G, Liu X, Liu Z and Su Z: Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema. Mol Med Rep 11: 1188-1194, 2015.
APA
Li, G., Liu, X., Liu, Z., & Su, Z. (2015). Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema. Molecular Medicine Reports, 11, 1188-1194. https://doi.org/10.3892/mmr.2014.2867
MLA
Li, G., Liu, X., Liu, Z., Su, Z."Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema". Molecular Medicine Reports 11.2 (2015): 1188-1194.
Chicago
Li, G., Liu, X., Liu, Z., Su, Z."Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema". Molecular Medicine Reports 11, no. 2 (2015): 1188-1194. https://doi.org/10.3892/mmr.2014.2867
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