3,3'-Diindolylmethane inhibits VEGF expression through the HIF-1α and NF-κB pathways in human retinal pigment epithelial cells under chemical hypoxic conditions

  • Authors:
    • Hongzoo Park
    • Dae-Sung Lee
    • Mi-Jin Yim
    • Yung Hyun Choi
    • Saegwang Park
    • Su-Kil Seo
    • Jung Sik Choi
    • Won Hee Jang
    • Sung Su Yea
    • Won Sun Park
    • Chang-Min Lee
    • Won-Kyo Jung
    • Il-Whan Choi
  • View Affiliations

  • Published online on: May 5, 2015     https://doi.org/10.3892/ijmm.2015.2202
  • Pages: 301-308
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Abstract

Oxidative stress in the retinal pigment epithelium (RPE) can lead to the pathological causes of age-related macular degeneration (AMD). Hypoxia induces oxidative damage in retinal pigment epithelial cells (RPE cells). In this study, we investigated the capacity of 3,3'-diindolylmethane (DIM) to reduce the expression of vascular endothelial growth factor (VEGF) under hypoxic conditions, as well as the molecular mechanisms involved. Human RPE cells (ARPE-19 cells) were treated with cobalt chloride (CoCl2, 200 µM) and/or DIM (10 and 20 µM). The production of VEGF was measured by enzyme-linked immunosorbent assay. The translocation of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-κB (NF-κB) was determined by western blot analysis. The binding activity of HIF-1α and NF-κB was analyzed by electrophoretic mobility shift assay. The phosphorylation levels of mitogen-activated protein kinases (MAPKs) were measured by western blot analysis. The levels of mitochondrial reactive oxygen species (ROS) were detected by fluorescence microplate assay. The results revealed that DIM significantly attenuated the CoCl2-induced expression of VEGF in the ARPE-19 cells. The CoCl2-induced translocation and activation of HIF-1α and NF-κB were also attenuated by treatment with DIM. In addition, DIM inhibited the CoCl2-induced activation of p38 MAPK in the ARPE-19 cells. Pre-treatment with YCG063, a mitochondrial ROS inhibitor, led to the downregulation of the CoCl2-induced production of VEGF by suppressing HIF-1α and NF-κB activity. Taken together, the findings of our study demonstrate that DIM inhibits the CoCl2-induced production of VEGF by suppressing mitochondrial ROS production, thus attenuating the activation of HIF-1α and p38 MAPK/NF-κB.
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July-2015
Volume 36 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Park H, Lee D, Yim M, Choi YH, Park S, Seo S, Choi JS, Jang WH, Yea SS, Park WS, Park WS, et al: 3,3'-Diindolylmethane inhibits VEGF expression through the HIF-1α and NF-κB pathways in human retinal pigment epithelial cells under chemical hypoxic conditions. Int J Mol Med 36: 301-308, 2015
APA
Park, H., Lee, D., Yim, M., Choi, Y.H., Park, S., Seo, S. ... Choi, I. (2015). 3,3'-Diindolylmethane inhibits VEGF expression through the HIF-1α and NF-κB pathways in human retinal pigment epithelial cells under chemical hypoxic conditions. International Journal of Molecular Medicine, 36, 301-308. https://doi.org/10.3892/ijmm.2015.2202
MLA
Park, H., Lee, D., Yim, M., Choi, Y. H., Park, S., Seo, S., Choi, J. S., Jang, W. H., Yea, S. S., Park, W. S., Lee, C., Jung, W., Choi, I."3,3'-Diindolylmethane inhibits VEGF expression through the HIF-1α and NF-κB pathways in human retinal pigment epithelial cells under chemical hypoxic conditions". International Journal of Molecular Medicine 36.1 (2015): 301-308.
Chicago
Park, H., Lee, D., Yim, M., Choi, Y. H., Park, S., Seo, S., Choi, J. S., Jang, W. H., Yea, S. S., Park, W. S., Lee, C., Jung, W., Choi, I."3,3'-Diindolylmethane inhibits VEGF expression through the HIF-1α and NF-κB pathways in human retinal pigment epithelial cells under chemical hypoxic conditions". International Journal of Molecular Medicine 36, no. 1 (2015): 301-308. https://doi.org/10.3892/ijmm.2015.2202