Projects per year
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.
Original language | English |
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Pages (from-to) | 354-362 |
Number of pages | 9 |
Journal | Redox Biology |
Volume | 8 |
Early online date | 7 Mar 2016 |
DOIs | |
Publication status | Published - Aug 2016 |
Keywords
- Poly (ADP-ribose) polymerase-1
- lens
- cataract
- DNA damage
- cell survival
- human
Profiles
Projects
- 2 Finished
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Humane Research Trust Laboratory
Wormstone, M., Sanderson, J., Evans-Gowing, R. & Russell, S.
1/01/14 → 31/12/16
Project: Research
Research output
- 31 Citations (Scopus)
- 1 Article
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Ku80 counters oxidative stress-induced DNA damage and cataract formation in the human lens
Smith, A. J. O., Ball, S. S. R., Manzar, K., Bowater, R. P. & Wormstone, I. M., Dec 2015, In: Investigative Ophthalmology and Visual Science. 56, 13, p. 7868-7874 7 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile20 Citations (Scopus)23 Downloads (Pure)