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DNA damage, poly(ADP-Ribose) polymerase activation, and phosphorylated histone H2AX expression during postnatal retina development in C57BL/6 mouse.

Authors :
Martín-Oliva D
Martín-Guerrero SM
Matia-González AM
Ferrer-Martín RM
Martín-Estebané M
Carrasco MC
Sierra A
Marín-Teva JL
Calvente R
Navascués J
Cuadros MA
Source :
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2015 Feb 03; Vol. 56 (2), pp. 1301-9. Date of Electronic Publication: 2015 Feb 03.
Publication Year :
2015

Abstract

Purpose: The purpose of this study was to investigate the incidence of DNA damage during postnatal development of the retina and the relationship between DNA damage and cell death.<br />Methods: DNA damage in the developing postnatal retina of C57BL/6 mice was assessed by determining the amounts of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is indicative of DNA oxidation and related to the formation of DNA single-strand breaks (SSBs), and phosphorylated histone H2AX (γ-H2AX), a marker of DNA double-strand breaks (DSBs). Poly(ADP-ribose) polymerase (PARP) activation was measured by ELISA and Western blotting. The location of γ-H2AX-positive and dying cells was determined by immunofluorescence and TUNEL assays.<br />Results: Oxidative DNA damage was maintained at low levels during high PARP activation between postnatal days 0 (P0) and P7. Phosphorylated histone H2AX gradually increased between P0 and P14 and decreased thereafter. Phosphorylated histone H2AX-positive cells with cell death morphology or TUNEL positivity were more abundant at P7 than at P14.<br />Conclusions: Oxidative DNA damage in postnatal retina increases during development. It is low during the first postnatal week when PARP-1 activity is high but increases thereafter. The rise in DSBs when PARP activity is downregulated may be attributable to accumulated oxidative damage and SSBs. At P7 and P14, γ-H2AX-positive cells are repairing naturally occurring DNA damage, but some are dying (mostly at P7), probably due to an accumulation of irreparable DNA damage.<br /> (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Details

Language :
English
ISSN :
1552-5783
Volume :
56
Issue :
2
Database :
MEDLINE
Journal :
Investigative ophthalmology & visual science
Publication Type :
Academic Journal
Accession number :
25650421
Full Text :
https://doi.org/10.1167/iovs.14-15828