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
December-2017 Volume 16 Issue 6

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
December-2017 Volume 16 Issue 6

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

Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway

  • Authors:
    • Xin Wang
    • Dalin Jia
    • Juncheng Zhang
    • Wei Wang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 9189-9196
    |
    Published online on: October 10, 2017
       https://doi.org/10.3892/mmr.2017.7756
  • 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 aim of the present study was to observe the protective effect of grape seed proanthocyanidins (GSPs) against endoplasmic reticulum (ER) stress‑mediated apoptosis caused by hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes along with its potential mechanisms. H9C2 cardiomyocytes underwent hypoxia for 3 h followed by reoxygenation for 3 h. Different doses of GSPs (50, 100 and 200 µg/ml) were administered 30 min before hypoxia. Cell viability was assessed, as well as lactic dehydrogenase (LDH) activity, cell apoptosis rate, expression levels of glucose‑regulated protein 78 (GRP78), C/EBP‑homologous protein (CHOP), protein kinase RNA‑like ER kinase (PERK), and eukaryotic translation initiation factor‑2 (eIF2α) mRNA and protein. The results revealed that GSPs improved cell viability, reduced LDH activity and reduced the apoptosis rate in cells subjected to H/R, and that the protective effect was most significant when 100 µg/ml in GSPs was administered. GSPs treatment also decreased mRNA and protein expression of GRP78, CHOP, eIF2α and the level of the phosphorylated form of PERK. Furthermore, GSPs displayed a similar protective effect to that of established ER stress inhibitor 4‑phenyl butyric acid. In conclusion, the findings of this study suggest that GSPs may protect H9C2 cardiomyocytes from H/R injury by decreasing ER stress‑mediated apoptosis through the suppression of the PERK/eIF2α signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Garcia-Dorado D: Myocardial reperfusion injury: A new view. Cardiovasc Res. 61:363–364. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Sharma V, Bell RM and Yellon DM: Targeting reperfusion injury in acute myocardial infarction: A review of reperfusion injury pharmacotherapy. Expert Opin Pharmacother. 13:1153–1175. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Bainey KR and Armstrong PW: Clinical perspectives on reperfusion injury in acute myocardial infarction. Am Heart J. 167:637–645. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Murry CE, Jennings RB and Reimer KA: Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation. 74:1124–1136. 1986. View Article : Google Scholar : PubMed/NCBI

5 

Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA and Vinten-Johansen J: Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 285:H579–H588. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Kalogeris T, Baines CP, Krenz M and Korthuis RJ: Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 298:229–317. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Stamboul K, Lorin J, Lorgis L, Guenancia C, Beer JC, Touzery C, Rochette L, Vergely C, Cottin Y and Zeller M: Atrial fibrillation is associated with a marker of endothelial function and oxidative stress in patients with acute myocardial infarction. PLoS One. 10:e01314392015. View Article : Google Scholar : PubMed/NCBI

8 

Logue SE, Cleary P, Saveljeva S and Samali A: New directions in ER stress-induced cell death. Apoptosis. 18:537–546. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Doroudgar S and Glembotski CC: New concepts of endoplasmic reticulum function in the heart: Programmed to conserve. J Mol Cell Cardiol. 55:85–91. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Schroder M and Kaufman RJ: The mammalian unfolded protein response. Annu Rev Biochem. 74:739–789. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Tabas I and Ron D: Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 13:184–190. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Boyce M and Yuan J: Cellular response to endoplasmic reticulum stress: A matter of life or death. Cell Death Differ. 13:363–373. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Kasseckert SA, Schäfer C, Kluger A, Gligorievski D, Tillmann J, Schlüter KD, Noll T, Sauer H, Piper HM and Abdallah Y: Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation. Cardiovasc Res. 83:381–387. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Bagchi D, Bagchi M, Stohs Sj, Ray SD, Sen CK and Preuss HG: Cellular protection with proanthocyanidins derived from grape seeds. Ann N Y Acad Sci. 957:260–270. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Kim TH, Jeon EJ, Cheung DY, Kim CW, Kim SS, Park SH, Han SW, Kim MJ, Lee YS, Cho ML, et al: Gastroprotective effects of grape seed proanthocyanidin extracts against nonsteroid anti-inflammatory drug-induced gastric injury in rats. Gut Liver. 7:282–289. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Ozkan G, Ulusoy S, Alkanat M, Orem A, Akcan B, Ersöz S, Yuluğ E, Kaynar K and Al S: Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity. Ren Fail. 34:460–466. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Singh T, Sharma SD and Katiyar SK: Grape proanthocyanidins induce apoptosis by loss of mitochondrial membrane potential of human non-small cell lung cancer cells in vitro and in vivo. PLoS One. 6:e274442011. View Article : Google Scholar : PubMed/NCBI

18 

Cheng M, Gao HQ, Xu L, Li BY, Zhang H and Li XH: Cardioprotective effects of grape seed proanthocyanidins extracts in streptozocin induced diabetic rats. J Cardiovasc Pharmacol. 50:503–509. 2007.PubMed/NCBI

19 

Gao Y, Jia P, Shu W and Jia D: The protective effect of lycopene on hypoxia/reoxygenation-induced endoplasmic reticulum stress in H9C2 cardiomyocytes. Eur J Pharmacol. 774:71–79. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Sun J, Sun G, Meng X, Wang H, Wang M, Qin M, Ma B, Luo Y, Yu Y, Chen R, et al: Ginsenoside RK3 prevents hypoxia-reoxygenation induced apoptosis in H9c2 cardiomyocytes via AKT and MAPK pathway. Evid Based Complement Alternat Med. 2013:6901902013. View Article : Google Scholar : PubMed/NCBI

22 

Yang Y, Duan W, Jin Z, Yi W, Yan J, Zhang S, Wang N, Liang Z, Li Y, Chen W, et al: JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury. J Pineal Res. 55:275–286. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Hou X, Han J, Yuan C, Ren H, Zhang Y, Zhang T, Xu L, Zheng Q and Chen W: Cardioprotective effects of total flavonoids extracted from xinjiang sprig rosa rugosa against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart. Cardiovasc Toxicol. 16:54–66. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Marklund S and Marklund G: Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 47:469–474. 1974. View Article : Google Scholar : PubMed/NCBI

25 

van Huizen R, Martindale JL, Gorospe M and Holbrook NJ: P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling. J Biol Chem. 278:15558–15564. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Ron D and Walter P: Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 8:519–529. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Rimm EB, Giovannucci EL, Willett WC, Colditz GA, Ascherio A, Rosner B and Stampfer MJ: Prospective study of alcohol consumption and risk of coronary disease in men. Lancet. 338:464–468. 1991. View Article : Google Scholar : PubMed/NCBI

28 

Sato M, Maulik G, Ray PS, Bagchi D and Das DK: Cardioprotective effects of grape seed proanthocyanidin against ischemic reperfusion injury. J Mol Cell Cardiol. 31:1289–1297. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Pataki T, Bak I, Kovacs P, Bagchi D, Das DK and Tosaki A: Grape seed proanthocyanidins improved cardiac recovery during reperfusion after ischemia in isolated rat hearts. Am J Clin Nutr. 75:894–899. 2002.PubMed/NCBI

30 

Zhao G, Gao H, Qiu J, Lu W and Wei X: The molecular mechanism of protective effects of grape seed proanthocyanidin extract on reperfusion arrhythmias in rats in vivo. Biol Pharm Bull. 33:759–767. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Shao ZH, Wojcik KR, Dossumbekova A, Hsu C, Mehendale SR, Li CQ, Qin Y, Sharp WW, Chang WT, Hamann KJ, et al: Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling. J Cell Biochem. 107:697–705. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Gao Z, Liu G, Hu Z and Li X, Yang X, Jiang B and Li X: Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis. Mol Med Rep. 9:801–807. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Liu CM, Ma JQ, Liu SS, Zheng GH, Feng ZJ and Sun JM: Proanthocyanidins improves lead-induced cognitive impairments by blocking endoplasmic reticulum stress and nuclear factor-κB-mediated inflammatory pathways in rats. Food Chem Toxicol. 72:295–302. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Sizlan A, Guven A, Uysal B, Yanarates O, Atim A, Oztas E, Cosar A and Korkmaz A: Proanthocyanidin protects intestine and remote organs against mesenteric ischemia/reperfusion injury. World J Surg. 33:1384–1391. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Xu ZC, Yin J, Zhou B, Liu YT, Yu Y and Li GQ: Grape seed proanthocyanidin protects liver against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress. World J Gastroenterol. 21:7468–7477. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang X, Jia D, Zhang J and Wang W: Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway. Mol Med Rep 16: 9189-9196, 2017.
APA
Wang, X., Jia, D., Zhang, J., & Wang, W. (2017). Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway. Molecular Medicine Reports, 16, 9189-9196. https://doi.org/10.3892/mmr.2017.7756
MLA
Wang, X., Jia, D., Zhang, J., Wang, W."Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway". Molecular Medicine Reports 16.6 (2017): 9189-9196.
Chicago
Wang, X., Jia, D., Zhang, J., Wang, W."Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway". Molecular Medicine Reports 16, no. 6 (2017): 9189-9196. https://doi.org/10.3892/mmr.2017.7756
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Jia D, Zhang J and Wang W: Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway. Mol Med Rep 16: 9189-9196, 2017.
APA
Wang, X., Jia, D., Zhang, J., & Wang, W. (2017). Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway. Molecular Medicine Reports, 16, 9189-9196. https://doi.org/10.3892/mmr.2017.7756
MLA
Wang, X., Jia, D., Zhang, J., Wang, W."Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway". Molecular Medicine Reports 16.6 (2017): 9189-9196.
Chicago
Wang, X., Jia, D., Zhang, J., Wang, W."Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway". Molecular Medicine Reports 16, no. 6 (2017): 9189-9196. https://doi.org/10.3892/mmr.2017.7756
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