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Open AccessArticle

All-Trans Retinoic Acid Modulates DNA Damage Response and the Expression of the VEGF-A and MKI67 Genes in ARPE-19 Cells Subjected to Oxidative Stress

1
Department of Molecular Genetics, University of Lodz, 90-236 Lodz, Poland
2
Department of Comparative Endocrinology, Medical University of Lodz, 90-752 Lodz, Poland
3
Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland
4
Department of Ophthalmology, Kuopio University Hospital, 70210 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Guillermo T. Sáez
Int. J. Mol. Sci. 2016, 17(6), 898; https://doi.org/10.3390/ijms17060898
Received: 31 March 2016 / Revised: 23 May 2016 / Accepted: 27 May 2016 / Published: 14 June 2016
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases)
Age-related macular degeneration (AMD) is characterized by the progressive degradation of photoreceptors and retinal pigment epithelium (RPE) cells. ARPE-19 is an RPE cell line established as an in vitro model for the study of AMD pathogenesis. Oxidative stress is an AMD pathogenesis factor that induces DNA damage. Thus, the oxidative stress-mediated DNA damage response (DDR) of ARPE-19 cells can be important in AMD pathogenesis. The metabolism of retinoids—which regulates cell proliferation, differentiation, and the visual cycle in the retina—was reported to be disturbed in AMD patients. In the present work, we studied the effect of all-trans retinoic acid (ATRA, a retinoid) on DDR in ARPE-19 cells subjected to oxidative stress. We observed that ATRA increased the level of reactive oxygen species (ROS), alkali-labile sites in DNA, DNA single-strand breaks, and cell death evoked by oxidative stress. ATRA did not modulate DNA repair or the distribution of cells in cell cycle in the response of ARPE-19 cells to oxidative stress. ATRA induced autophagy in the absence of oxidative stress, but had no effect on this process in the stress. ATRA induced over-expression of proliferation marker MKI67 and neovascularization marker VEGF-A. In conclusion, ATRA increased oxidative stress in ARPE-19 cells, resulting in more lesions to their DNA and cell death. Moreover, ATRA can modulate some properties of these cells, including neovascularization, which is associated with the exudative form of AMD. Therefore, ATRA can be important in the prevention, diagnosis, and therapy of AMD. View Full-Text
Keywords: AMD; ARPE-19 cells; ATRA; cell death; DDR; DNA damage response; oxidative stress; retinoic acid; ROS AMD; ARPE-19 cells; ATRA; cell death; DDR; DNA damage response; oxidative stress; retinoic acid; ROS
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MDPI and ACS Style

Tokarz, P.; Piastowska-Ciesielska, A.W.; Kaarniranta, K.; Blasiak, J. All-Trans Retinoic Acid Modulates DNA Damage Response and the Expression of the VEGF-A and MKI67 Genes in ARPE-19 Cells Subjected to Oxidative Stress. Int. J. Mol. Sci. 2016, 17, 898. https://doi.org/10.3390/ijms17060898

AMA Style

Tokarz P, Piastowska-Ciesielska AW, Kaarniranta K, Blasiak J. All-Trans Retinoic Acid Modulates DNA Damage Response and the Expression of the VEGF-A and MKI67 Genes in ARPE-19 Cells Subjected to Oxidative Stress. International Journal of Molecular Sciences. 2016; 17(6):898. https://doi.org/10.3390/ijms17060898

Chicago/Turabian Style

Tokarz, Paulina; Piastowska-Ciesielska, Agnieszka W.; Kaarniranta, Kai; Blasiak, Janusz. 2016. "All-Trans Retinoic Acid Modulates DNA Damage Response and the Expression of the VEGF-A and MKI67 Genes in ARPE-19 Cells Subjected to Oxidative Stress" Int. J. Mol. Sci. 17, no. 6: 898. https://doi.org/10.3390/ijms17060898

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