Skip to main content
SpringerLink
Log in

Role of Pigment Epithelium-Derived Factor (PEDF) in Arsenic-Induced Cell Apoptosis of Liver and Brain in a Rat Model

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Tondel M, Rahman M, Magnuson A et al (1999) The relationship of arsenic levels in drinking water and the prevalence rate of skin lesions in Bangladesh. Environ Health Perspect 107:727–729

    Article  PubMed  CAS  Google Scholar 

  2. Yu G, Sun DJ, Zheng Y (2007) Health effects of exposure to natural arsenic in groundwater and coal in China: an overview of occurrence. Environ Health Perspect 115:636–642

    Article  PubMed  CAS  Google Scholar 

  3. Sun G, Li FJ, Li GX et al (1998) The exploration for the mechanism of arsenic on kidney toxicity in mice. Chin J Endemiol 17:284–286

    CAS  Google Scholar 

  4. Sun G (2007) The progress on the mechanism research of drinking-type endemic arsenism. J Med Res 36:2–4

    Google Scholar 

  5. Bashir S, Sharma Y, Irshad M et al (2006) Arsenic induced apoptosis in rat liver following repeated 60 days exposure. Toxicology 217:63–70

    Article  PubMed  CAS  Google Scholar 

  6. Namgung U, Xia Z (2001) Arsenic induces apoptosis in rat cerebellar neurons via activation of JNK3 and p38 MAP kinases. Toxicol Appl Pharmacol 174:130–138

    Article  PubMed  CAS  Google Scholar 

  7. Qu W, Bortner CD, Sakurai T et al (2002) Acquisition of apoptotic resistance in arsenic-induced malignant transformation: role of the JNK signal transduction pathway. Carcinogenesis 23:151–159

    Article  PubMed  CAS  Google Scholar 

  8. Shi Y, Wei Y, Qu S et al (2010) Arsenic induces apoptosis of human umbilical vein endothelial cells through mitochondrial pathways. Cardiovasc Toxicol 10:153–160

    Article  PubMed  CAS  Google Scholar 

  9. Zhi F, Wang XG (2011) Arsenite-induced apoptosis is prevented by selenitein A375 cell line. Biol Trace Elem Res 140:7–17

    Article  Google Scholar 

  10. Liu J, Michael P (2008) Liver is a target of arsenic carcinogenesis. Toxicol Sci 105:24–32

    Article  PubMed  CAS  Google Scholar 

  11. Tombran-Tink J, Chader GG, Johnson LV et al (1991) PEDF: pigment epithelium-derived factor with potent neuronal differentiative activity. Exp Eye Res 53:411–414

    Article  PubMed  CAS  Google Scholar 

  12. Ek E, Dass CR, Chong PF (2006) PEDF: a potential molecular therapeutic target with multiple anticancer activities. Trends Mol Med 12:497–502

    Article  PubMed  CAS  Google Scholar 

  13. Zhao LJ, Gao YH, Li YY et al (2012) Differential expression of serum proteins in chronic arsenic exposed population. Chin J Endemiol 31:7–12

    Google Scholar 

  14. Liu J, Liu Y, Goyer RA (2000) Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oral or injected inorganic arsenicals. Toxicol Sci 55:460–467

    Article  PubMed  CAS  Google Scholar 

  15. Majhi C, Khan S, Leo MD et al (2011) Effects of acetaminophen on reactive oxygen species and nitric oxide redox signaling in kidney of arsenic-exposed rats. Food Chem Toxicol 49:974–982

    Article  PubMed  CAS  Google Scholar 

  16. Huang M, Choi SJ, Kim DW et al (2009) Risk assessment of low-level cadmium and arsenic on the kidney. J Toxicol Environ Health A72:1493–1498

    Article  Google Scholar 

  17. Wang J, Zhang W, Sun DJ et al (2010) Analysis of neuroglobin mRNA expression in rat Brain due to arsenite-induced oxidative stress. Environ Toxicol. doi:10.1002/tox.20664

  18. Abe R, Shimizu T, Yamagishi S et al (2004) Over expression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. Am J Pathol 164:1225–1232

    Article  PubMed  CAS  Google Scholar 

  19. Amano S, Yamagishi S, Inagaki Y et al (2005) Pigment epitheliumderived factor inhibits oxidative stress-induced apoptosis and dysfunction of cultured retinal pericytes. Microvasc Res 69:45–55

    Article  PubMed  CAS  Google Scholar 

  20. Garcia M, Fernandez-Garcia NI, Rivas V et al (2004) Inhibition of xenografted human melanoma growth and prevention of metastasis development by dual antiangiogenic/antitumor activities of pigment epithelium-derived factor. Cancer Res 64:5632–5642

    Article  PubMed  CAS  Google Scholar 

  21. Kawaguchi T, Yamagishi S, Itou M et al (2010) Pigment epithelium-derived factor inhibits lysosomal degradation of Bcl-xL and apoptosis in HepG2 cells. Am J Pathol 176:168–176

    Article  PubMed  CAS  Google Scholar 

  22. Yamagishi S, Inagaki Y, Amano S et al (2002) Pigment epithelium derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its anti-oxidative properties. Biochem Biophys Res Commun 296:877–882

    Article  PubMed  CAS  Google Scholar 

  23. Zhang T, Guan M, Xu C et al (2007) Pigment epithelium-derived factor inhibits glioma cell growth in vitro and in vivo. Life Sci 81:1256–1263

    Article  PubMed  CAS  Google Scholar 

  24. Shimizu S, Ide T, Yanagida T et al (2000) Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c. J Biol Chem 275:12321–12325

    Article  PubMed  CAS  Google Scholar 

  25. Mikhailov V, Mikhailova M, Degenhardt K et al (2003) Association of Bax and Bak homo-oligomers in mitochondria Bax requirement for Bak reorganization and cytochrome C release. J Biol Chem 278:5367–5376

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the 11th Five-Year Planning Project of Science and Technology Supporting (project no. 2006BAI06B04), Ministry of Science and Technology, China.

Conflict of interest

There are no conflicts of interest for any of the authors.

Author information

Authors and Affiliations

  1. Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China

    Wei Zhang, Hongqi Feng, Yanhui Gao, Liyan Sun, Jing Wang, Yuanyuan Li, Cheng Wang, Lijun Zhao, Xinxin Hu, Huixin Sun & Dianjun Sun

  2. Key Laboratory of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province & Ministry of Health, 157 Baojian Road, Harbin, 150081, China

    Wei Zhang, Hongqi Feng, Yanhui Gao, Liyan Sun, Jing Wang, Yuanyuan Li, Cheng Wang, Lijun Zhao, Xinxin Hu, Huixin Sun & Dianjun Sun

  3. Department of Community Medicine, Mercer University School of Medicine, Macon, GA, 31207, USA

    Yudan Wei

Authors
  1. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongqi Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanhui Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liyan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuanyuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lijun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xinxin Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Huixin Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yudan Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Dianjun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yudan Wei or Dianjun Sun.

Additional information

Wei Zhang, Hongqi Feng and Yanhui Gao contributed equally to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, W., Feng, H., Gao, Y. et al. Role of Pigment Epithelium-Derived Factor (PEDF) in Arsenic-Induced Cell Apoptosis of Liver and Brain in a Rat Model. Biol Trace Elem Res 151, 269–276 (2013). https://doi.org/10.1007/s12011-012-9558-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-012-9558-7

Keywords

Search

Navigation