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
August-2020 Volume 22 Issue 2

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
August-2020 Volume 22 Issue 2

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

Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress

  • Authors:
    • Jie Cui
    • Cheng Cao
    • Huan Hu
    • Hao Zhang
    • Yujing Yang
    • Luqiao Wang
    • Xiao Huang
    • Ping Li
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
  • Pages: 1631-1638
    |
    Published online on: June 2, 2020
       https://doi.org/10.3892/mmr.2020.11204
  • 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

Elevated plasma homocysteine (Hcy) levels are associated with endothelial dysfunction. Previous studies have indicated the role of endoplasmic reticulum (ER) stress in Hcy‑induced endothelial injury. However, the mechanism of action remains unclear. In the current study, the role of human folate receptor α (hFRα) in Hcy‑induced ER stress was investigated, along with endothelial injury in human umbilical vein endothelial cells (HUVECs). The results showed that a moderate dose of Hcy induced morphological injury and reduced viability of HUVECs. Furthermore, moderate‑dose Hcy reduced hFRα expression in HUVECs. Notably, hFRα inhibition by RNA interference resulted in activation of the protein kinase RNA‑like endoplasmic reticulum kinase pathway and increased apoptosis of HUVECs. In conclusion, this study demonstrated the presence of hFRα in HUVECs, and indicated its role in the regulation of ER stress and cell injury by Hcy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Han L, Wu Q, Wang C, Hao Y, Zhao J, Zhang L, Fan R, Liu Y, Li R, Chen Z, et al: Homocysteine, ischemic stroke, and coronary heart disease in hypertensive patients: a population-based, prospective cohort study. Stroke. 46:1777–1786. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Bonetti PO, Lerman LO and Lerman A: Endothelial dysfunction: A marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 23:168–175. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Vita JA: Endothelial function. Circulation. 124:e906–e912. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Stamler JS, Osborne JA, Jaraki O, Rabbani LE, Mullins M, Singel D and Loscalzo J: Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest. 91:308–318. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Woo KS, Chook P, Lolin YI, Cheung AS, Chan LT, Sun YY, Sanderson JE, Metreweli C and Celermajer DS: Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation. 96:2542–2544. 1997. View Article : Google Scholar : PubMed/NCBI

6 

Cimellaro A, Perticone M, Fiorentino TV, Sciacqua A and Hribal ML: Role of endoplasmic reticulum stress in endothelial dysfunction. Nutr Metab Cardiovasc Dis. 26:863–871. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Wang XC, Sun WT, Yu CM, Pun SH, Underwood MJ, He GW and Yang Q: ER stress mediates homocysteine-induced endothelial dysfunction: Modulation of IKCa and SKCa channels. Atherosclerosis. 242:191–198. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Zhang Z, Wei C, Zhou Y, Yan T, Wang Z, Li W and Zhao L: Homocysteine induces apoptosis of human umbilical vein endothelial cells via mitochondrial dysfunction and endoplasmic reticulum stress. Oxid Med Cell Longev. 2017:57365062017. View Article : Google Scholar : PubMed/NCBI

9 

De Bree A, Verschuren WM, Kromhout D, Kluijtmans LA and Blom HJ: Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease. Pharmacol Rev. 54:599–618. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Casas JP, Bautista LE, Smeeth L, Sharma P and Hingorani AD: Homocysteine and stroke: Evidence on a causal link from mendelian randomisation. Lancet. 365:224–232. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, et al CSPPT Investigators, : Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: The CSPPT randomized clinical trial. JAMA. 313:1325–1335. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ and Schouten EG; MTHFR Studies Collaboration Group, : MTHFR 677C-->T polymorphism and risk of coronary heart disease: A meta-analysis. JAMA. 288:2023–2031. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Mark SD, Wang W, Fraumeni JF Jr, Li JY, Taylor PR, Wang GQ, Guo W, Dawsey SM, Li B and Blot WJ: Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: The Linxian Nutrition Intervention Trial. Am J Epidemiol. 143:658–664. 1996. View Article : Google Scholar : PubMed/NCBI

14 

Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong EL, Xu HE and Melcher K: Structural basis for molecular recognition of folic acid by folate receptors. Nature. 500:486–489. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Parker N, Turk MJ, Westrick E, Lewis JD, Low PS and Leamon CP: Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem. 338:284–293. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Weitman SD, Weinberg AG, Coney LR, Zurawski VR, Jennings DS and Kamen BA: Cellular localization of the folate receptor: Potential role in drug toxicity and folate homeostasis. Cancer Res. 52:6708–6711. 1992.PubMed/NCBI

17 

Hou Z and Matherly LH: Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr. 73:175–204. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH and Goldman ID: Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. 127:917–928. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Harding HP, Zhang Y, Bertolotti A, Zeng H and Ron D: Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell. 5:897–904. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Cui S, Li W, Wang P, Lv X, Gao Y and Huang G: Folic acid inhibits homocysteine-induced cell apoptosis in human umbilical vein endothelial cells. Mol Cell Biochem. 444:77–86. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Wu X, Zhang L, Miao Y, Yang J, Wang X, Wang CC, Feng J and Wang L: Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis. Redox Biol. 20:46–59. 2019. View Article : Google Scholar : PubMed/NCBI

23 

Bao XM, Wu CF and Lu GP: Atorvastatin attenuates homocysteine-induced apoptosis in human umbilical vein endothelial cells via inhibiting NADPH oxidase-related oxidative stress-triggered p38MAPK signaling. Acta Pharmacol Sin. 30:1392–1398. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Zhu L, Jia F, Wei J, Yu Y, Yu T, Wang Y, Sun J and Luo G: Salidroside protects against homocysteine-induced injury in human umbilical vein endothelial cells via the regulation of endoplasmic reticulum stress. Cardiovasc Ther. 35:33–39. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Blum A, Hijazi I, Eizenberg MM and Blum N: Homocysteine (Hcy) follow-up study. Clin Invest Med. 30:21–25. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Perna AF, Lanza D, Sepe I, Conzo G, Altucci L and Ingrosso D: Altered folate receptor 2 expression in uraemic patients on haemodialysis: Implications for folate resistance. Nephrol Dial Transplant. 28:1214–1224. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Hotamisligil GS: Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 140:900–917. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cui J, Cao C, Hu H, Zhang H, Yang Y, Wang L, Huang X and Li P: Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress. Mol Med Rep 22: 1631-1638, 2020.
APA
Cui, J., Cao, C., Hu, H., Zhang, H., Yang, Y., Wang, L. ... Li, P. (2020). Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress. Molecular Medicine Reports, 22, 1631-1638. https://doi.org/10.3892/mmr.2020.11204
MLA
Cui, J., Cao, C., Hu, H., Zhang, H., Yang, Y., Wang, L., Huang, X., Li, P."Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress". Molecular Medicine Reports 22.2 (2020): 1631-1638.
Chicago
Cui, J., Cao, C., Hu, H., Zhang, H., Yang, Y., Wang, L., Huang, X., Li, P."Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress". Molecular Medicine Reports 22, no. 2 (2020): 1631-1638. https://doi.org/10.3892/mmr.2020.11204
Copy and paste a formatted citation
x
Spandidos Publications style
Cui J, Cao C, Hu H, Zhang H, Yang Y, Wang L, Huang X and Li P: Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress. Mol Med Rep 22: 1631-1638, 2020.
APA
Cui, J., Cao, C., Hu, H., Zhang, H., Yang, Y., Wang, L. ... Li, P. (2020). Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress. Molecular Medicine Reports, 22, 1631-1638. https://doi.org/10.3892/mmr.2020.11204
MLA
Cui, J., Cao, C., Hu, H., Zhang, H., Yang, Y., Wang, L., Huang, X., Li, P."Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress". Molecular Medicine Reports 22.2 (2020): 1631-1638.
Chicago
Cui, J., Cao, C., Hu, H., Zhang, H., Yang, Y., Wang, L., Huang, X., Li, P."Downregulation of folate receptor α contributes to homocysteine‑induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress". Molecular Medicine Reports 22, no. 2 (2020): 1631-1638. https://doi.org/10.3892/mmr.2020.11204
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