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Human RPE expression of cell survival factors.

Publication ,  Journal Article
Yang, P; Wiser, JL; Peairs, JJ; Ebright, JN; Zavodni, ZJ; Bowes Rickman, C; Jaffe, GJ
Published in: Invest Ophthalmol Vis Sci
May 2005

PURPOSE: To determine basal and tumor necrosis factor (TNF)-alpha-regulated expression of retinal pigment epithelial (RPE) cell survival factors and whether regulation is dependent on nuclear transcription factor (NF)-kappaB. METHODS: Cultured human RPE cells were infected with adenovirus encoding either mutant inhibitory (I)-kappaB or beta-galactosidase and treated with TNF-alpha for various times. Freshly prepared RPE/choroid and RPE samples were isolated from human donor eyes. Real-time reverse transcription-polymerase chain reaction, Western blot, and immunocytochemistry were used to determine survival factor gene expression, cellular protein levels, and localization, respectively. RESULTS: Multiple survival factor genes, including cellular inhibitor of apoptosis protein (c-IAP1), c-IAP2, TNF receptor-associated factor-1 (TRAF-1), TRAF-2, B-cell leukemia/lymphoma-2 (Bcl-2), Bcl-x, A1, and cellular Fas-associated death domain (FADD)-like interleukin-1beta-converting enzyme-like inhibitory protein (c-FLIP), were expressed in basal conditions in both cultured RPE cells and RPE cells in situ, whereas survivin was expressed only by cultured cells. TNF-alpha upregulated expression of TRAF-1, TRAF-2, c-IAP1, c-IAP2, c-FLIP, and A1. TRAF-1, c-FLIP, and to a lesser extent c-IAP2 protein levels were increased by TNF-alpha in a time-dependent manner, whereas c-IAP1, survivin, Bcl-x(L), and TRAF-2 protein levels were not influenced by TNF-alpha treatment at any time point tested. In contrast, Bcl-2 and A1 proteins were not detected under basal conditions or after TNF-alpha treatment. Overexpression of mutant IkappaB blocked TNF-alpha-induced TRAF-1, TRAF-2, c-IAP1, c-IAP2, c-FLIP, and A1 gene expression and downregulated TRAF-1 protein levels. TRAF-1 and Bcl-x(L) proteins were localized diffusely in RPE cytoplasm. CONCLUSIONS: Multiple RPE cell survival factors are expressed by human RPE cells. TNF-alpha regulates expression of some of these factors in an NF-kappaB-dependent manner, whereas others are not influenced by NF-kappaB. RPE cell survival factors may protect RPE cells from apoptosis normally and in diseases such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR).

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

May 2005

Volume

46

Issue

5

Start / End Page

1755 / 1764

Location

United States

Related Subject Headings

  • bcl-X Protein
  • Ubiquitin-Protein Ligases
  • Tumor Necrosis Factor-alpha
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 1
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-bcl-2
  • Proteins
  • Pigment Epithelium of Eye
  • Ophthalmology & Optometry
 

Citation

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ICMJE
MLA
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Yang, P., Wiser, J. L., Peairs, J. J., Ebright, J. N., Zavodni, Z. J., Bowes Rickman, C., & Jaffe, G. J. (2005). Human RPE expression of cell survival factors. Invest Ophthalmol Vis Sci, 46(5), 1755–1764. https://doi.org/10.1167/iovs.04-1039
Yang, Ping, Jessica L. Wiser, James J. Peairs, Jessica N. Ebright, Zachary J. Zavodni, Catherine Bowes Rickman, and Glenn J. Jaffe. “Human RPE expression of cell survival factors.Invest Ophthalmol Vis Sci 46, no. 5 (May 2005): 1755–64. https://doi.org/10.1167/iovs.04-1039.
Yang P, Wiser JL, Peairs JJ, Ebright JN, Zavodni ZJ, Bowes Rickman C, et al. Human RPE expression of cell survival factors. Invest Ophthalmol Vis Sci. 2005 May;46(5):1755–64.
Yang, Ping, et al. “Human RPE expression of cell survival factors.Invest Ophthalmol Vis Sci, vol. 46, no. 5, May 2005, pp. 1755–64. Pubmed, doi:10.1167/iovs.04-1039.
Yang P, Wiser JL, Peairs JJ, Ebright JN, Zavodni ZJ, Bowes Rickman C, Jaffe GJ. Human RPE expression of cell survival factors. Invest Ophthalmol Vis Sci. 2005 May;46(5):1755–1764.

Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

May 2005

Volume

46

Issue

5

Start / End Page

1755 / 1764

Location

United States

Related Subject Headings

  • bcl-X Protein
  • Ubiquitin-Protein Ligases
  • Tumor Necrosis Factor-alpha
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 1
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-bcl-2
  • Proteins
  • Pigment Epithelium of Eye
  • Ophthalmology & Optometry