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
November-2017 Volume 16 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-2017 Volume 16 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

Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway

  • Authors:
    • Lu Zou
    • Xiaoyan Li
    • Nan Wu
    • Pengyu Jia
    • Chunting Liu
    • Dalin Jia
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, The Core Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 6934-6939
    |
    Published online on: August 31, 2017
       https://doi.org/10.3892/mmr.2017.7404
  • 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

Increased free fatty acids in cardiomyocytes induce myocardial lipotoxic injury, but the underlying mechanisms are not well understood. Therefore, the aim of the present study was to explore the role of the endoplasmic reticulum (ER) stress‑mediated apoptosis pathway in palmitate (PA)‑induced cardiomyocyte lipotoxicity. H9c2 cells were treated with various doses (100, 200 and 400 µM) of PA to mimic cardiomyocyte lipotoxicity in vitro. Oil Red O staining was used to determine the accumulation of intracellular lipids. An MTT assay was used to determine the cell viability. Lactate dehydrogenase (LDH) activity was used to measure the injury of H9c2 cells. Flow cytometry analysis was used to detect apoptosis. Western blotting was used to evaluate the expression change of ER stress‑mediated apoptosis pathway proteins, including 78 kDa glucose‑regulated protein (GRP78), eukaryotic initiation factor 2 α (eIF2α), protein kinase R‑like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP) and cleaved caspase‑12. The results demonstrated that various doses of PA promoted excessive lipid deposition in cardiomyocytes and resulted in decreased cell viability, and increased the LDH activity and apoptosis rate in a dose‑dependent manner. Furthermore, the expression of GRP78, a marker of ER stress, and the phosphorylation of eIF2α and PERK were increased following treatment with PA. Notably, the levels of CHOP and cleaved caspase‑12, critical regulators of ER stress‑mediated apoptosis pathway, were also elevated, and this effect was reversed by a specific ER stress inhibitor (4‑phenyl butyric acid). In conclusion, the results of the current study demonstrated that PA induces myocardial lipotoxic injury by triggering ER stress and the ER stress‑mediated apoptosis pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Ussher JR: The role of cardiac lipotoxicity in the pathogenesis of diabetic cardiomyopathy. Expert Rev Cardiovasc Ther. 12:345–358. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Carley AN and Severson DL: Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biochim Biophys Acta. 1734:112–126. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Gambert S, Vergely C, Filomenko R, Moreau D, Bettaieb A, Opie LH and Rochette L: Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts. Mol Cell Biochem. 283:147–152. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Wei CD, Li Y, Zheng HY, Tong YQ and Dai W: Palmitate induces H9c2 cell apoptosis by increasing reactive oxygen species generation and activation of the ERK1/2 signaling pathway. Mol Med Rep. 7:855–861. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Phillips MJ and Voeltz GK: Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol. 17:69–82. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Groenendyk J, Sreenivasaiah PK, Kim DH, Agellon LB and Michalak M: Biology of endoplasmic reticulum stress in the heart. Circ Res. 107:1185–1197. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Sano R and Reed JC: ER stress-induced cell death mechanisms. Biochim Biophys Acta. 1833:3460–3470. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Listenberger LL, Ory DS and Schaffer JE: Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J Biol Chem. 276:14890–14895. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Haffar T, Bérubé-Simard FA and Bousette N: Cardiomyocyte lipotoxicity is mediated by Il-6 and causes down-regulation of PPARs. Biochem Biophys Res Commun. 459:54–59. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Cao J, Dai DL, Yao L, Yu HH, Ning B, Zhang Q, Chen J, Cheng WH, Shen W and Yang ZX: Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway. Mol Cell Biochem. 364:115–129. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Lai E, Bikopoulos G, Wheeler MB, Rozakis-Adcock M and Volchuk A: Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic beta-cells. Am J Physiol Endocrinol Metab. 294:E540–E550. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Yin J, Wang Y, Gu L, Fan N, Ma Y and Peng Y: Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation. Int J Mol Med. 35:932–940. 2015. View Article : Google Scholar : PubMed/NCBI

13 

van Rooy MJ and Pretorius E: Obesity, hypertension and hypercholesterolemia as risk factors for atherosclerosis leading to ischemic events. Curr Med Chem. 21:2121–2129. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Wende AR and Abel ED: Lipotoxicity in the heart. Biochim Biophys Acta. 1801:311–319. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Goldberg IJ, Trent CM and Schulze PC: Lipid metabolism and toxicity in the heart. Cell Metab. 15:805–812. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Wei CD, Li Y, Zheng HY, Sun KS, Tong YQ, Dai W, Wu W and Bao AY: Globular adiponectin protects H9c2 cells from palmitate-induced apoptosis via Akt and ERK1/2 signaling pathways. Lipids Health Dis. 11:1352012. View Article : Google Scholar : PubMed/NCBI

17 

López-Hernández B, Ceña V and Posadas I: The endoplasmic reticulum stress and the HIF-1 signalling pathways are involved in the neuronal damage caused by chemical hypoxia. Br J Pharmacol. 172:2838–2851. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Chen S, Melchior WB Jr and Guo L: Endoplasmic reticulum stress in drug- and environmental toxicant-induced liver toxicity. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 32:83–104. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Cui Y, Zhao D, Barrow PA and Zhou X: The endoplasmic reticulum stress response: A link with tuberculosis? Tuberculosis (Edinb). 97:52–56. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Chistiakov DA, Sobenin IA, Orekhov AN and Bobryshev YV: Role of endoplasmic reticulum stress in atherosclerosis and diabetic macrovascular complications. Biomed Res Int. 2014:6101402014. View Article : Google Scholar : PubMed/NCBI

21 

Guo XF and Yang XJ: Endoplasmic reticulum stress response in spontaneously hypertensive rats is affected by myocardial ischemia reperfusion injury. Exp Ther Med. 9:319–326. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Wang J, Hu X and Jiang H: ER stress-induced apoptosis: A novel therapeutic target in heart failure. Int J Cardiol. 177:564–565. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Jing G, Wang JJ and Zhang SX: ER stress and apoptosis: A new mechanism for retinal cell death. Exp Diabetes Res. 2012:5895892012. View Article : Google Scholar : PubMed/NCBI

24 

Park M, Sabetski A, Chan Y Kwan, 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
Zou L, Li X, Wu N, Jia P, Liu C and Jia D: Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway. Mol Med Rep 16: 6934-6939, 2017.
APA
Zou, L., Li, X., Wu, N., Jia, P., Liu, C., & Jia, D. (2017). Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway. Molecular Medicine Reports, 16, 6934-6939. https://doi.org/10.3892/mmr.2017.7404
MLA
Zou, L., Li, X., Wu, N., Jia, P., Liu, C., Jia, D."Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway". Molecular Medicine Reports 16.5 (2017): 6934-6939.
Chicago
Zou, L., Li, X., Wu, N., Jia, P., Liu, C., Jia, D."Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway". Molecular Medicine Reports 16, no. 5 (2017): 6934-6939. https://doi.org/10.3892/mmr.2017.7404
Copy and paste a formatted citation
x
Spandidos Publications style
Zou L, Li X, Wu N, Jia P, Liu C and Jia D: Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway. Mol Med Rep 16: 6934-6939, 2017.
APA
Zou, L., Li, X., Wu, N., Jia, P., Liu, C., & Jia, D. (2017). Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway. Molecular Medicine Reports, 16, 6934-6939. https://doi.org/10.3892/mmr.2017.7404
MLA
Zou, L., Li, X., Wu, N., Jia, P., Liu, C., Jia, D."Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway". Molecular Medicine Reports 16.5 (2017): 6934-6939.
Chicago
Zou, L., Li, X., Wu, N., Jia, P., Liu, C., Jia, D."Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress‑mediated apoptosis pathway". Molecular Medicine Reports 16, no. 5 (2017): 6934-6939. https://doi.org/10.3892/mmr.2017.7404
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