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Article

Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death

  • Authors:
    • Haibo Jiang
    • Siqi Xiong
    • Xiaobo Xia
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China
  • Pages: 1737-1742
    |
    Published online on: February 26, 2014
       https://doi.org/10.3892/mmr.2014.1987
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Abstract

Retinitis pigmentosa (RP) is a group of inherited diseases that primarily affect light‑sensitive rods and cones in the retina. Rhodopsin mutations, including the T17M mutation, are associated with the autosomal dominant form of retinitis pigmentosa (ADRP) and have been linked to abnormal protein folding. However, the molecular mechanisms underlying T17M rhodopsin‑induced retinal degeneration are yet to be elucidated. In the present study, Human embryonic kidney (HEK) 293 and ARPE‑19 cells were transfected with myc‑tagged wild‑type (WT) and T17M rhodopsin constructs. Cells were fixed and stained with anti‑myc antibodies and the localization of WT and T17M rhodopsin was visualized using immunofluorescence microscopy. Turnover rates of WT and T17M rhodopsin were measured using western blot analysis. In addition, endoplasmic reticulum (ER) stress‑induced cell death was analyzed in WT and T17M rhodopsin‑transfected cells using nuclear staining. Misfolded T17M rhodopsin was observed to be abnormally localized in the ER, while WT rhodopsin was predominantly found at the plasma membrane. Protein turnover analysis revealed that T17M rhodopsin was more rapidly degraded by proteasomes than WT rhodopsin. Furthermore, overexpression of T17M rhodopsin was observed to induce cell death and increase cytotoxicity; predisposing cells to ER stress‑induced cell death. These findings show novel insight into the properties of T17M rhodopsin and highlight the role of ER stress in T17M‑associated RP.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang H, Xiong S and Xia X: Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death. Mol Med Rep 9: 1737-1742, 2014.
APA
Jiang, H., Xiong, S., & Xia, X. (2014). Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death. Molecular Medicine Reports, 9, 1737-1742. https://doi.org/10.3892/mmr.2014.1987
MLA
Jiang, H., Xiong, S., Xia, X."Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death". Molecular Medicine Reports 9.5 (2014): 1737-1742.
Chicago
Jiang, H., Xiong, S., Xia, X."Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death". Molecular Medicine Reports 9, no. 5 (2014): 1737-1742. https://doi.org/10.3892/mmr.2014.1987
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang H, Xiong S and Xia X: Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death. Mol Med Rep 9: 1737-1742, 2014.
APA
Jiang, H., Xiong, S., & Xia, X. (2014). Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death. Molecular Medicine Reports, 9, 1737-1742. https://doi.org/10.3892/mmr.2014.1987
MLA
Jiang, H., Xiong, S., Xia, X."Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death". Molecular Medicine Reports 9.5 (2014): 1737-1742.
Chicago
Jiang, H., Xiong, S., Xia, X."Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death". Molecular Medicine Reports 9, no. 5 (2014): 1737-1742. https://doi.org/10.3892/mmr.2014.1987
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