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
May-2018 Volume 17 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
May-2018 Volume 17 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 Open Access

PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R

  • Authors:
    • Yiqian Zhang
    • Yufeng Li
    • Zhiwei Liu
    • Qixiang Zhao
    • Hao Zhang
    • Xiaoyu Wang
    • Peng Lu
    • Hongli Yu
    • Meng Wang
    • Hongyan Dong
    • Zhongming Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Thoracic Cardiovascular Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China, Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 7170-7176
    |
    Published online on: March 14, 2018
       https://doi.org/10.3892/mmr.2018.8733
  • 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

Pigment epithelial-derived factor (PEDF) is a multifunctional secreted glycoprotein, which exerts a variety of physiological activities. PEDF may protect against hypoxia‑induced cell death associated with its antioxidative effects and p53 mitochondrial translocation in cultured cardiomyocytes and H9c2 cells. Additionally, previous studies have suggested that autophagy is an important cell survival mechanism. However, the effect of PEDF on autophagy and the associated pathway in hypoxic H9c2 cells has not been fully established. Autophagy has been reported to regulate lipid metabolism; however, little is known about whether PEDF is able to regulate lipid metabolism by promoting autophagy. In the present study, western blotting results revealed that PEDF increased the level of microtubule‑associated protein 1A/1B‑light chain 3 (LC3)‑II. Transmission electron microscopy (TEM) and LC3 fluorescence demonstrated that PEDF increased the number of autophagosomes. PEDF also increased the viability of hypoxic H9c2 cells and decreased the level of cleaved caspase‑3 protein, as evidenced by CCK‑8 assays and western blotting, respectively. TEM and a triglyceride assay kit demonstrated that PEDF‑induced autophagy may stimulate lipid degradation. Western blotting results revealed a novel mechanism underlying PEDF‑induced H9c2 cell autophagy via the PEDF‑R‑mediated Atg5 pathway under hypoxic conditions. Furthermore, the results also suggest that PEDF‑induced autophagy may stimulate lipid degradation. The survival function of autophagy suggests that modulation of PEDF‑induced autophagy may be used as a therapeutic strategy to protect cells against lipid-associated metabolic diseases.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Brookheart RT, Michel CI and Schaffer JE: As a matter of fat. Cell Metab. 10:9–12. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Huss JM, Levy FH and Kelly DP: Hypoxia inhibits the peroxisome proliferator-activated receptor alpha/retinoid X receptor gene regulatory pathway in cardiac myocytes: A mechanism for O2-dependent modulation of mitochondrial fatty acid oxidation. J Biol Chem. 276:27605–27612. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Chiu HC, Kovacs A, Ford DA, Hsu FF, Garcia R, Herrero P, Saffitz JE and Schaffer JE: A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest. 107:813–822. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Kawaguchi T, Yamagishi SI and Sata M: Structure-function relationships of PEDF. Curr Mol Med. 10:302–311. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Gao X, Zhang H, Zhuang W, Yuan G, Sun T, Jiang X, Zhou Z, Yuan H, Zhang Z and Dong H: PEDF and PEDF-derived peptide 44mer protect cardiomyocytes against hypoxia-induced apoptosis and necroptosis via anti-oxidative effect. Sci Rep. 4:56372014. View Article : Google Scholar : PubMed/NCBI

6 

Wang X, Zhang Y, Lu P, Zhang H, Li Y, Dong H and Zhang Z: PEDF attenuates hypoxia-induced apoptosis and necrosis in H9c2 cells by inhibiting p53 mitochondrial translocation via PEDF-R. Biochem Biophys Res Commun. 465:394–401. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Klionsky DJ: Autophagy: From phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 8:931–937. 2007. View Article : Google Scholar : PubMed/NCBI

8 

He C and Klionsky DJ: Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 43:67–93. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Hammond EM, Brunet CL, Johnson GD, Parkhill J, Milner AE, Brady G, Gregory CD and Grand RJ: Homology between a human apoptosis specific protein and the product of APG5, a gene involved in autophagy in yeast. FEBS Lett. 425:391–395. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Notari L, Baladron V, Aroca-Aguilar JD, Balko N, Heredia R, Meyer C, Notario PM, Saravanamuthu S, Nueda ML, Sanchez-Sanchez F, et al: Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. J Biol Chem. 281:38022–38037. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Zhang H, Sun T, Jiang X, Yu H, Wang M, Wei T, Cui H, Zhuang W, Liu Z, Zhang Z and Dong H: PEDF and PEDF-derived peptide 44mer stimulate cardiac triglyceride degradation via ATGL. J Transl Med. 13:682015. View Article : Google Scholar : PubMed/NCBI

12 

Subramanian P, Locatelli-Hoops S, Kenealey J, DesJardin J, Notari L and Becerra SP: Pigment epithelium-derived factor (PEDF) prevents retinal cell death via PEDF Receptor (PEDF-R): Identification of a functional ligand binding site. J Biol Chem. 288:23928–23942. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A and Zechner R: Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 306:1383–1386. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Haemmerle G, Moustafa T, Woelkart G, Büttner S, Schmidt A, van de Weijer T, Hesselink M, Jaeger D, Kienesberger PC, Zierler K, et al: ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1. Nat Med. 17:1076–1085. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Zhang H, Wang Z, Feng SJ, Xu L, Shi HX, Chen LL, Yuan GD, Yan W, Zhuang W, Zhang YQ, et al: PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis. Int J Mol Sci. 16:5618–5634. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM and Czaja MJ: Autophagy regulates lipid metabolism. Nature. 458:1131–1135. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Mizushima N, Ohsumi Y and Yoshimori T: Autophagosome formation in mammalian cells. Cell Struct Funct. 27:421–429. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Viventi J and Blanco JA: Development of high resolution, multiplexed electrode arrays: Opportunities and challenges. Conf Proc IEEE Eng Med Biol Soc. 2012:pp. 1394–1396. 2012; PubMed/NCBI

21 

van Herpen NA and Schrauwen-Hinderling VB: Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav. 94:231–241. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Chavez JA and Summers SA: Lipid oversupply, selective insulin resistance and lipotoxicity: Molecular mechanisms. Biochim Biophys Acta. 1801:252–265. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Tan SH, Shui G, Zhou J, Li JJ, Bay BH, Wenk MR and Shen HM: Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin). J Biol Chem. 287:14364–14376. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Kroemer G, Mariño G and Levine B: Autophagy and the integrated stress response. Mol Cell. 40:280–293. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Sutton MG and Sharpe N: Left ventricular remodeling after myocardial infarction: Pathophysiology and therapy. Circulation. 101:2981–2988. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Xuan H, Xue W, Pan J, Sha J, Dong B and Huang Y: Downregulation of miR-221, −30d and −15a contributes to pathogenesis of prostate cancer by targeting Bmi-1. Biochemistry (Mosc). 80:276–283. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Ma X, Liu H, Murphy JT, Foyil SR, Godar RJ, Abuirqeba H, Weinheimer CJ, Barger PM and Diwan A: Regulation of the transcription factor EB-PGC1α axis by beclin-1 controls mitochondrial quality and cardiomyocyte death under stress. Mol Cell Biol. 35:956–976. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Park M, Sabetski A, Kwan Chan Y, Turdi S and Sweeney G: Palmitate induces ER stress and autophagy in H9c2 cells: Implications for apoptosis and adiponectin resistance. J Cell Physiol. 230:630–639. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Li Y, Liu Z, Zhao Q, Zhang H, Wang X, Lu P, Yu H, Wang M, Dong H, Dong H, et al: PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R. Mol Med Rep 17: 7170-7176, 2018.
APA
Zhang, Y., Li, Y., Liu, Z., Zhao, Q., Zhang, H., Wang, X. ... Zhang, Z. (2018). PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R. Molecular Medicine Reports, 17, 7170-7176. https://doi.org/10.3892/mmr.2018.8733
MLA
Zhang, Y., Li, Y., Liu, Z., Zhao, Q., Zhang, H., Wang, X., Lu, P., Yu, H., Wang, M., Dong, H., Zhang, Z."PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R". Molecular Medicine Reports 17.5 (2018): 7170-7176.
Chicago
Zhang, Y., Li, Y., Liu, Z., Zhao, Q., Zhang, H., Wang, X., Lu, P., Yu, H., Wang, M., Dong, H., Zhang, Z."PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R". Molecular Medicine Reports 17, no. 5 (2018): 7170-7176. https://doi.org/10.3892/mmr.2018.8733
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Li Y, Liu Z, Zhao Q, Zhang H, Wang X, Lu P, Yu H, Wang M, Dong H, Dong H, et al: PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R. Mol Med Rep 17: 7170-7176, 2018.
APA
Zhang, Y., Li, Y., Liu, Z., Zhao, Q., Zhang, H., Wang, X. ... Zhang, Z. (2018). PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R. Molecular Medicine Reports, 17, 7170-7176. https://doi.org/10.3892/mmr.2018.8733
MLA
Zhang, Y., Li, Y., Liu, Z., Zhao, Q., Zhang, H., Wang, X., Lu, P., Yu, H., Wang, M., Dong, H., Zhang, Z."PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R". Molecular Medicine Reports 17.5 (2018): 7170-7176.
Chicago
Zhang, Y., Li, Y., Liu, Z., Zhao, Q., Zhang, H., Wang, X., Lu, P., Yu, H., Wang, M., Dong, H., Zhang, Z."PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R". Molecular Medicine Reports 17, no. 5 (2018): 7170-7176. https://doi.org/10.3892/mmr.2018.8733
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