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
September-2015 Volume 12 Issue 3

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
September-2015 Volume 12 Issue 3

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

DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway

  • Authors:
    • Yu-Feng Yan
    • Wen-Jie Yang
    • Qiang Xu
    • He-Ping Chen
    • Xiao-Shan Huang
    • Ling-Yu Qiu
    • Zhang-Ping Liao
    • Qi-Ren Huang
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Jiangxi Nursing Vocational and Technical College, Nanchang, Jiangxi 330006, P.R. China
  • Pages: 4734-4742
    |
    Published online on: June 17, 2015
       https://doi.org/10.3892/mmr.2015.3947
  • 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

DJ-1 protein, as a multifunctional intracellular protein, has an important role in transcriptional regulation and anti-oxidant stress. A recent study by our group showed that DJ-1 can regulate the expression of certain anti‑oxidant enzymes and attenuate hypoxia/re‑oxygenation (H/R)‑induced oxidative stress in the cardiomyocyte cell line H9c2; however, the detailed molecular mechanisms have remained to be elucidated. Nuclear factor erythroid 2‑like 2 (Nrf2) is an essential transcription factor that regulates the expression of several anti‑oxidant genes via binding to the anti‑oxidant response element (ARE). The present study investigated whether activation of the Nrf2 pathway is responsible for the induction of anti‑oxidative enzymes by DJ‑1 and contributes to the protective functions of DJ‑1 against H/R‑induced oxidative stress in H9c2 cells. The results demonstrated that DJ‑1‑overexpressing H9c2 cells exhibited anti‑oxidant enzymes, including manganese superoxide dismutase, catalase and glutathione peroxidase, to a greater extent and were more resistant to H/R‑induced oxidative stress compared with native cells, whereas DJ‑1 knockdown suppressed the induction of these enzymes and further augmented the oxidative stress injury. Determination of the importance of Nrf2 in DJ‑1‑mediated anti‑oxidant enzymes induction and cytoprotection against oxidative stress induced by H/R showed that overexpression of DJ‑1 promoted the dissociation of Nrf2 from its cytoplasmic inhibitor Keap1, resulting in enhanced levels of nuclear translocation, ARE‑binding and transcriptional activity of Nrf2. Of note, Nrf2 knockdown abolished the DJ‑1‑mediated induction of anti‑oxidant enzymes and cytoprotection against oxidative stress induced by H/R. In conclusion, these findings indicated that activation of the Nrf2 pathway is a critical mechanism by which DJ-1 upregulates anti-oxidative enzymes and attenuates H/R-induced oxidative stress in H9c2 cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Dhalla NS, Temsah RM and Netticadan T: Role of oxidative stress in cardiovascular diseases. J Hypertens. 18:655–673. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M and Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 39:44–84. 2007. View Article : Google Scholar

3 

Marczin N, El-Habashi N, Hoare GS, Bundy RE and Yacoub M: Antioxidants in myocardial ischemia-reperfusion injury: Therapeutic potential and basic mechanisms. Arch Biochem Biophys. 420:222–236. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Venardos KM, Perkins A, Headrick J and Kaye DM: Myocardial ischemia-reperfusion injury, antioxidant enzyme systems and selenium: A review. Curr Med Chem. 14:1539–1549. 2007. View Article : Google Scholar

5 

Nagakubo D, Taira T, Kitaura H, Ikeda M, Tamai K, Iguchi-Ariga SM and Ariga H: DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. Biochem Biophys Res Commun. 231:509–513. 1997. View Article : Google Scholar : PubMed/NCBI

6 

Ishikawa S, Taira T, Takahashi-Niki K, Niki T, Ariga H and Iguchi-Ariga SM: Human DJ-1-specific transcriptional activation of tyrosine hydroxylase gene. J Biol Chem. 285:39718–39731. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Shinbo Y, Taira T, Niki T, Iguchi-Ariga SM and Ariga H: DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3. Int J Oncol. 26:641–648. 2005.PubMed/NCBI

8 

Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K and Ariga H: DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep. 5:213–218. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Shendelman S, Jonason A, Martinat C, Leete T and Abeliovich A: DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation. PLoS Biol. 2:e3622004. View Article : Google Scholar : PubMed/NCBI

10 

Honbou K, Suzuki NN, Horiuchi M, Niki T, Taira T, Ariga H and Inagaki F: The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease. J Biol Chem. 278:31380–31384. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Yu HH, Xu Q, Chen HP, Wang S, Huang XS, Huang QR and He M: Stable overexpression of DJ-1 protects H9c2 cells against oxidative stress under a hypoxia condition. Cell Biochem Funct. 31:643–651. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Kaspar JW, Niture SK and Jaiswal AK: Nrf2: INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med. 47:1304–1309. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Nguyen T, Nioi P and Pickett CB: The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 284:13291–13295. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Keum YS and Choi BY: Molecular and chemical regulation of the Keap1-Nrf2 signaling pathway. Molecules. 19:10074–10089. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Sun Z, Zhang S, Chan JY and Zhang DD: Keap1 controls postin-duction repression of the Nrf2-mediated antioxidant response by escorting nuclear export of Nrf2. Mol Cell Biol. 27:6334–6349. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Howden R: Nrf2 and cardiovascular defense. Oxid Med Cell Longev. 2013:1043082013. View Article : Google Scholar : PubMed/NCBI

17 

Lee JM and Johnson JA: An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol. 37:139–143. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Clements CM, McNally RS, Conti BJ, Mak TW and Ting JP: DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc Natl Acad Sci USA. 103:15091–15096. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Huang XS, Chen HP, Yu HH, Yan YF, Liao ZP and Huang QR: Nrf2-dependent upregulation of antioxidative enzymes: A novel pathway for hypoxic preconditioning-mediated delayed cardio-protection. Mol Cell Biochem. 385:33–41. 2014. View Article : Google Scholar

20 

Perrelli MG, Pagliaro P and Penna C: Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species. World J Cardiol. 3:186–200. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Dongworth RK, Mukherjee UA, Hall AR, Astin R, Ong SB, Yao Z, Dyson A, Szabadkai G, Davidson SM, Yellon DM, et al: DJ-1 protects against cell death following acute cardiac ischemia-reperfusion injury. Cell Death Dis. 5:e10822014. View Article : Google Scholar : PubMed/NCBI

22 

Yanagisawa D, Kitamura Y, Inden M, Takata K, Taniguchi T, Morikawa S, Morita M, Inubushi T, Tooyama I, Taira T, et al: DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats. J Cereb Blood Flow Metab. 28:563–578. 2008. View Article : Google Scholar

23 

Inden M, Taira T, Kitamura Y, Yanagida T, Tsuchiya D, Takata K, Yanagisawa D, Nishimura K, Taniguchi T, Kiso Y, et al: PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model. Neurobiol Dis. 24:144–158. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Aleyasin H, Rousseaux MW, Phillips M, Kim RH, Bland RJ, Callaghan S, Slack RS, During MJ, Mak TW and Park DS: The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage. Proc Natl Acad Sci USA. 104:18748–18753. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Malhotra D, Thimmulappa R, Navas-Acien A, Sandford A, Elliott M, Singh A, Chen L, Zhuang X, Hogg J, Pare P, et al: Expression of concern: Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am J Respir Crit Care Med. 178:592–604. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Ustariz CR, Arce S, Hernández P, Almaguer M, Pérez S and Ballester JM: HLA antigens in paroxysmal nocturnal hemoglo-binuria. Acta Haematol. 63:52–54. 1980. View Article : Google Scholar

27 

Sun Z, Chin YE and Zhang DD: Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response. Mol Cell Biol. 29:2658–2672. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Sun Z, Huang Z and Zhang DD: Phosphorylation of Nrf2 at multiple sites by MAP kinases has a limited contribution in modulating the Nrf2-dependent antioxidant response. PLoS One. 4:e65882009. View Article : Google Scholar : PubMed/NCBI

29 

Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM and Ariga H: DJBP: A novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex and DJ-1 antagonizes this inhibition by abrogation of this complex. Mol Cancer Res. 1:247–261. 2003.PubMed/NCBI

30 

Takahashi K, Taira T, Niki T, Seino C, Iguchi-Ariga SM and Ariga H: DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor. J Biol Chem. 276:37556–37563. 2001. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yan Y, Yang W, Xu Q, Chen H, Huang X, Qiu L, Liao Z and Huang Q: DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway. Mol Med Rep 12: 4734-4742, 2015.
APA
Yan, Y., Yang, W., Xu, Q., Chen, H., Huang, X., Qiu, L. ... Huang, Q. (2015). DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway. Molecular Medicine Reports, 12, 4734-4742. https://doi.org/10.3892/mmr.2015.3947
MLA
Yan, Y., Yang, W., Xu, Q., Chen, H., Huang, X., Qiu, L., Liao, Z., Huang, Q."DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway". Molecular Medicine Reports 12.3 (2015): 4734-4742.
Chicago
Yan, Y., Yang, W., Xu, Q., Chen, H., Huang, X., Qiu, L., Liao, Z., Huang, Q."DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway". Molecular Medicine Reports 12, no. 3 (2015): 4734-4742. https://doi.org/10.3892/mmr.2015.3947
Copy and paste a formatted citation
x
Spandidos Publications style
Yan Y, Yang W, Xu Q, Chen H, Huang X, Qiu L, Liao Z and Huang Q: DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway. Mol Med Rep 12: 4734-4742, 2015.
APA
Yan, Y., Yang, W., Xu, Q., Chen, H., Huang, X., Qiu, L. ... Huang, Q. (2015). DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway. Molecular Medicine Reports, 12, 4734-4742. https://doi.org/10.3892/mmr.2015.3947
MLA
Yan, Y., Yang, W., Xu, Q., Chen, H., Huang, X., Qiu, L., Liao, Z., Huang, Q."DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway". Molecular Medicine Reports 12.3 (2015): 4734-4742.
Chicago
Yan, Y., Yang, W., Xu, Q., Chen, H., Huang, X., Qiu, L., Liao, Z., Huang, Q."DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway". Molecular Medicine Reports 12, no. 3 (2015): 4734-4742. https://doi.org/10.3892/mmr.2015.3947
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