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-2014 Volume 8 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-2014 Volume 8 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

Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin

  • Authors:
    • Liang Wang
    • Zhiyong Liu
    • Zhe Dong
    • Jieyi Pan
    • Xiaochun Ma
  • View Affiliations / Copyright

    Affiliations: Department of Intensive Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 1473-1478
    |
    Published online on: August 29, 2014
       https://doi.org/10.3892/etm.2014.1939
  • 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

Heparin is a potent blood anticoagulant that has been demonstrated to attenuate inflammatory responses in sepsis. Sepsis is considered to be a ­microcirculation‑mitochondrial distress syndrome. Azurocidin (AZU), a protein with strong heparin‑binding potential that induces inflammatory responses and apoptosis, has been shown to increase the permeability of endothelial cells and induce the prognosis of sepsis. However, the function of AZU in mitochondrial oxygen metabolism has yet to be reported. The aim of the present study was to investigate whether heparin exhibits an antagonistic effect on AZU‑induced mitochondrial dysfunction in human umbilical vein endothelial cells (HUVECs) and to further investigate the possible underlying mechanisms. HUVECs were randomly assigned into blank control, AZU, heparin plus AZU and heparin groups. The blank control group were incubated with phosphate‑buffered saline for 12 h, while the AZU group were incubated with 1 µg/ml AZU for 12 h. The heparin plus AZU group were incubated with 100 µg/ml heparin for 2 h, followed by the addition of 1 µg/ml AZU and incubation for 12 h. The heparin group were incubated with 100 µg/ml heparin for 12 h. Flow cytometry was used to determine the mitochondrial membrane potential, while electron microscopy was used to determine the mitochondrial morphology. Western blotting and quantitative polymerase chain reaction were used to determine the protein and mRNA expression levels of Cox II in the mitochondria, respectively. Western blotting was also used to evaluate the concentration of AZU in cytoplasm, along with immunofluorescence analysis. AZU was revealed to decrease the mitochondrial membrane potential, reduce cytochrome c oxidase subunit II expression and destroy the morphology of the mitochondria. Heparin exhibited an antagonistic function on these processes and inhibited the endocytosis of AZU by HUVECs. In conclusion, the results indicated that AZU inhibited the oxygen metabolic function in mitochondria, and this function was effectively antagonized by heparin via the inhibition of AZU endocytosis by HUVECs. Therefore, heparin may be a potential therapeutic agent for treating mitochondrial dysfunction in the future.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Mu E, Ding R, An X, et al: Heparin attenuates lipopolysaccharide-induced acute lung injury by inhibiting nitric oxide synthase and TGF-β/Smad signaling pathway. Thromb Res. 129:479–485. 2012.

2 

Zhao D, Ding R, Mao Y, et al: Heparin rescues sepsis-associated acute lung injury and lethality through the suppression of inflammatory responses. Inflammation. 35:1825–1832. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Ding R, Zhao D, Guo R, Zhang Z and Ma X: Treatment with unfractionated heparin attenuates coagulation and inflammation in endotoxemic mice. Thromb Res. 128:e160–e165. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Han J, Ding R, Zhao D, Zhang Z and Ma X: Unfractionated heparin attenuates lung vascular leak in a mouse model of sepsis: role of RhoA/Rho kinase pathway. Thromb Res. 132:e42–e47. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Levy MM, Fink MP, Marshall JC, et al; International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 29:530–538. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Garrabou G, Morén C, López S, et al: The effects of sepsis on mitochondria. J Infect Dis. 205:392–400. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Spronk PE, Kanoore-Edul VS and Ince C: Microcirculatory and mitochondrial distress syndrome (MMDS): A new look at sepsis. Functional Hemodynamic Monitoring. Pinsky MR and Payden D: 42. Springer; Berlin: pp. 47–67. 2005, View Article : Google Scholar

8 

Totsukawa G, Yamakita Y, Yamashiro S, et al: Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J Cell Biol. 150:797–806. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Rasmussen PB, Bjørn S, Hastrup S, et al: Characterization of recombinant human HBP/CAP37/azurocidin, a pleiotropic mediator of inflammation-enhancing LPS-induced cytokine release from monocytes. FEBS Lett. 390:109–112. 1996. View Article : Google Scholar : PubMed/NCBI

10 

Olofsson AM, Vestberg M, Herwald H, et al: Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis. J Clin Invest. 104:885–894. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Mai S, Klinkenberg M, Auburger G, Bereiter-Hahn J and Jendrach M: Decreased expression of Drp1 and Fis1 mediates mitochondrial elongation in senescent cells and enhances resistance to oxidative stress through PINK1. J Cell Sci. 123:917–926. 2010. View Article : Google Scholar

12 

Chew MS, Linder A, Santen S, et al: Increased plasma levels of heparin-binding protein in patients with shock: a prospective, cohort study. Inflamm Res. 61:375–379. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Holub M and Beran O: Should heparin-binding protein levels be routinely monitored in patients with severe sepsis and septic shock? Crit Care. 16:1332012.PubMed/NCBI

14 

Linder A, Akesson P, Inghammar M, et al: Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock. Critical Care. 16:R902012. View Article : Google Scholar : PubMed/NCBI

15 

Tapper H, Karlsson A, Morgelin M, Flodgaard H and Herwald H: Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles. Blood. 99:1785–1793. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Flodgaard H, Ostergaard E, Bayne S, et al: Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities. Eur J Biochem. 197:535–547. 1991. View Article : Google Scholar

17 

Nieuwdorp M, Meuwese MC, Vink H, et al: The endothelial glycocalyx: a potential barrier between health and vascular disease. Curr Opin Lipidol. 16:507–511. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Arfors KE, Lundberg C, Lindbom L, et al: A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 69:338–340. 1987.

19 

Chertov O, Ueda H, Xu LL, et al: Identification of human neutrophil-derived cathepsin G and azurocidin/CAP37 as chemoattractants for mononuclear cells and neutrophils. J Exp Med. 186:739–747. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Soehnlein O, Xie X, Ulbrich H, et al: Neutrophil-derived heparin-binding protein (HBP/CAP37) deposited on endothelium enhances monocyte arrest under flow conditions. J Immunol. 174:6399–6405. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Lunemann JD, Buttgereit F, Tripmacher R, et al: Norepinephrine inhibits energy metabolism of human peripheral blood mononuclear cells via adrenergic receptors. Biosci Rep. 21:627–635. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Perry AJ, Rimmer KA, Mertens HD, et al: Structure, topology and function of the translocase of the outer membrane of mitochondria. Plant Physiol Biochem. 46:265–274. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang L, Liu Z, Dong Z, Pan J and Ma X: Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin. Exp Ther Med 8: 1473-1478, 2014.
APA
Wang, L., Liu, Z., Dong, Z., Pan, J., & Ma, X. (2014). Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin. Experimental and Therapeutic Medicine, 8, 1473-1478. https://doi.org/10.3892/etm.2014.1939
MLA
Wang, L., Liu, Z., Dong, Z., Pan, J., Ma, X."Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin". Experimental and Therapeutic Medicine 8.5 (2014): 1473-1478.
Chicago
Wang, L., Liu, Z., Dong, Z., Pan, J., Ma, X."Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin". Experimental and Therapeutic Medicine 8, no. 5 (2014): 1473-1478. https://doi.org/10.3892/etm.2014.1939
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Liu Z, Dong Z, Pan J and Ma X: Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin. Exp Ther Med 8: 1473-1478, 2014.
APA
Wang, L., Liu, Z., Dong, Z., Pan, J., & Ma, X. (2014). Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin. Experimental and Therapeutic Medicine, 8, 1473-1478. https://doi.org/10.3892/etm.2014.1939
MLA
Wang, L., Liu, Z., Dong, Z., Pan, J., Ma, X."Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin". Experimental and Therapeutic Medicine 8.5 (2014): 1473-1478.
Chicago
Wang, L., Liu, Z., Dong, Z., Pan, J., Ma, X."Azurocidin‑induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin". Experimental and Therapeutic Medicine 8, no. 5 (2014): 1473-1478. https://doi.org/10.3892/etm.2014.1939
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