PARP-1 inhibition influences the oxidative stress response of the human lens

Smith, Andrew, Ball, Simon, Bowater, Richard ORCID: https://orcid.org/0000-0002-2745-7807 and Wormstone, Ian ORCID: https://orcid.org/0000-0002-6423-7766 (2016) PARP-1 inhibition influences the oxidative stress response of the human lens. Redox Biology, 8. pp. 354-362. ISSN 2213-2317

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Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) is best characterised for its involvement in DNA repair. PARP-1 activity is also linked to cell fate, confounding its roles in maintaining genome integrity. The current study assessed the functional roles of PARP-1 within human lens cells in response to oxidative stress. The human lens epithelial cell line FHL124 and whole human lens cultures were used as experimental systems. Hydrogen peroxide (H2O2) was employed to induce oxidative stress and cell death was assessed by LDH release. The functional influence of PARP-1 was assessed using targeted siRNA and chemical inhibition (by AG14361). Immunocytochemistry and western blotting were used to assess PARP-1 expression and the alkaline comet assay determined the levels of DNA strand breaks. PARP-1 was generally observed in the cell nucleus in both the FHL124 cell line and whole human lenses. PARP-1 inhibition rendered FHL124 cells more susceptible to H2O2-induced DNA strand breaks. Interestingly, reduction of PARP-1 activity significantly inhibited H2O2-induced cell death relative to control cells. Inhibition of PARP-1 in whole human lenses resulted in a reduced level of lens opacity and cell death following exposure to H2O2 relative to matched pair controls. Thus, we show that PARP-1 could play a role in the fate of human lens cells, and these first observations in human lenses suggest that it could impact on lens opacity. Further studies are required to elucidate the regulatory processes that give rise to these effects.

Item Type:	Article
Additional Information:	© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords:	poly (adp-ribose) polymerase-1,lens,cataract,dna damage,cell survival,human
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Science > School of Natural Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Cells and Tissues Faculty of Science > Research Groups > Molecular Microbiology Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry Faculty of Science > Research Groups > Biosciences Teaching and Education Research
Depositing User:	Pure Connector
Date Deposited:	17 Mar 2016 11:01
Last Modified:	12 May 2023 00:04
URI:	https://ueaeprints.uea.ac.uk/id/eprint/57513
DOI:	10.1016/j.redox.2016.03.003

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