April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
The Effect of SUN N8075 on Endoplasmic Reticulum Stress-Induced Cell Death in RGC-5 Cells
Author Affiliations & Notes
  • M. Shimazawa
    Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan
  • R. Uchibayashi
    Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan
  • K. Tsuruma
    Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan
  • H. Hara
    Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5466. doi:
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      M. Shimazawa, R. Uchibayashi, K. Tsuruma, H. Hara; The Effect of SUN N8075 on Endoplasmic Reticulum Stress-Induced Cell Death in RGC-5 Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5466.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Retinal ganglion cell (RGC) death has been reported to occur via a variety of mechanisms involving oxidative stress, endoplasmic reticulum (ER) stress, and ischemia. In the present study, we evaluated the protective effect of SUN N8075 {(2S)-1-(4-amino-2,3,5-trimethylphenoxy)-3-[4-[4-(4-fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate}, a dual Na+ and Ca2+ channel blocker with antioxidant activity, on ER stress-induced cell death in RGC-5, a neuronal precursor cell line that can be differentiated to resemble retinal ganglion cells.

Methods: : RGC-5 damage was induced by tunicamycin (an ER stress inducer), serum deprivation, or buthionine sulfoximine (BSO) with glutamate (oxidative stress). Cell viability was measured by resazurin assay or double nuclear stainings (Hoechst 33342 and YO-PRO-1). Levels of glucose-regulated protein (GRP) 78/BiP, an ER-resident molecular chaperon, and C/EBP-homologous protein (CHOP), a member of the CCAAT/enhancer-binding protein family, were analyzed by immunoblot. Furthermore, caspase 3/7 activity was measured using Caspase-Glo 3/7 Assay Kit. SUN N8075 (0.3 to 10 µM), trolox (soluble vitamin E analogue; 30 and 100 µM), or edaravone (neuroprotective antioxidant; 1 to 10 µM) was treated 1 h prior to tunicamycin application.

Results: : SUN N8075 inhibited RGC-5 cell death induced by tunicamycin, serum deprivation, and BSO/glutamate. Trolox and edaravone also inhibited the cell death induced by serum deprivation and BSO/glutamate, but did not tunicamycin-induced cell death. Furthermore, SUN N8075 inhibited tunicamycin-induced caspase 3/7 activation. On the other hand, SUN N8075 did not affect the increase of GRP78 or CHOP protein induced by tunicamycin.

Conclusions: : These findings suggest that SUN N8075 may be one of the potential therapeutic candidates for ophthalmic disorders.

Keywords: neuroprotection • apoptosis/cell death • cell survival 
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