Yokota, T., Igarashi, K., Uchihara, T., Jishage, K., Tomita, H., Inaba, A., Li, Y., Arita, M., Suzuki, H., Mizusawa, H. and Aria, H. (2001) Delayed-Onset Ataxia in Mice Lacking Alpha-Tocopherol Transfer Protein: Model for Neuronal Degeneration Caused by Chronic Oxidative Stress. Proceedings of the National Academy of Sciences of the United States of America, 98, 15185-15190.
http://dx.doi.org/10.1073/pnas.261456098

has been cited by the following article:

• TITLE: Modulation of Oxidative Stress Responses by Vitamin E, or Vitamin A plus Vitamin C Treatment in Human Retinal Pigment Epithelial Cells

  AUTHORS: Jinggang Yin, Christina S. Winborn, Fridtjof Thomas, Quynh T. Tran, John C. Lang, Edward Chaum

  KEYWORDS: Vitamin Supplementation, AP1 Transcription Factors, Oxidative Stress, Retinal Pigment Epithelium, Age-Related Macular Degeneration

  JOURNAL NAME: Natural Science, Vol.7 No.12, November 25, 2015

  ABSTRACT: The purpose of this study was to characterize the potential of vitamins to protect the retinal pig-ment epithelium (RPE) from oxidative stress (OS). We have previously shown that OS induces the expression of AP1 transcription factors (FOSB, CFOS and ATF3), but is modulated by pretreatment with vitamin C (200 μM). We propose that OS-induced AP1 expression can be used as a biomarker of OS to test the efficacy of vitamins to limit the impact of OS in the RPE. Here we examined the efficacy of vitamin E or combined vitamin A plus vitamin C to modulate OS-induced AP1 expression in the RPE. We pretreated human ARPE-19 cells with vitamin E (0 - 7.5 μM) or with combined vitamin A (10 or 15 μM) plus vitamin C (50 or 100 μM) for 3 days prior to exposure to 500 μM H2O2 OS for 1 - 4 h. AP1 expression was assessed using qRT-PCR. Pretreatment with ≥2.5 μM vitamin E significantly decreased OS-induced AP1 expression at 1 - 4 h OS, compared to controls. Lower doses of vitamin E were ineffective at modulating OS responses. Pretreatment with 100 μM vitamin C combined with 15 μM vitamin A protected RPE cells from OS-induced AP1 expression. There is an additive and potentially protective effect of 100 μM vitamin C and 15 μM vitamin A on FOSB expression at 4 h, and a potentially protective effect of 100 μM vitamin C and 15 μM vitamin A on CFOS expression at 1 h OS. A protective effect was also seen with 15 μM vitamin A pretreatment alone on ATF3 expression. Thus, “sub-therapeutic” levels of multiple vitamins may protect RPE cells better than higher doses of a single vitamin. This OS-induced AP1 expression biomarker assay may be useful to identify complex antioxidant formulations as therapeutics for degenerative diseases that are thought to be caused by OS, like age-related macular degeneration.