Enhancing cell viability after UV exposure: the effects of antioxidants, flavonoids and PARP inhibitors.
Exposure to ultraviolet radiation (UVR) is associated with skin aging, skin diseases and the development of various skin cancers, including melanoma1. It is capable of directly and indirectly damaging many important cellular macromolecules, including DNA, proteins and lipids.
Much of this damage is associated with free radicals, and the induction of an oxidative stress environment. Upon exposure to UVR, free radical activity within the cell is enhanced. When this activity outweighs the cell’s natural defences and repair capacity, the cell sustains damage and is said to be in a state of oxidative stress.
PARP (poly[ADP-ribose] polymerase) is an enzyme involved in the repair of DNA damage, such as that caused by UVR. It uses NAD+, a ubiquitous molecule important in many other cellular processes2, to produce polymers that assist in the DNA repair. In cases of massive DNA damage however, PARP may be overactivated and deplete cellular NAD+ levels such that other NAD+-dependent processes (such as energy production and the activity of the sirtuin “longevity genes”) cannot continue3.
PARP inhibition is currently under clinical investigation for the treatment of stroke, vascular disease and other conditions associated with oxidative injury4. It is thought this approach is effective as it allows for the maintenance of NAD+, although this is at the expense of DNA repair.
Flavonoids are a class of plant-based, polyphenolic compounds frequently reported to protect against forms of oxidative damage5. Many act as antioxidants, mopping up the free radicals before they are able to damage the cell. Others, such as the grape-derived resveratrol, have been reported to maintain NAD+ levels through periods of oxidative damage6.
As such, this study will investigate the effects of antioxidants, flavonoids and PARP inhibitors upon cell viability after UVR exposure in an attempt to identify the most effective approach to maintain cellular health and viability in situations of oxidative stress.
- To investigate the effect of selected flavonoid treatments and PARP inhibitors on cell viability, DNA repair and NAD+ levels following UV damage
- Ichihashi M, Ueda M, Budiyanta A, Bito T, Oka M, Fukunaga M et al (2003). UV-induced skin damage. Toxicology 189, 21-39
- Belenky P, Bogan K, Brenner C (2006). NAD+ metabolism in health and disease. Trends Biochem Sci 32, 12-19
- Park J, Halliday G, Surjana D, Damian D (2010). Nicotinamide prevents ultraviolet radiation-induced cellular energy loss. Photochem Photobiol 86, 942-948
- Peralta-Leal A, Rodriguez-Vargas J, Aguillar-Quesada R, Rodriguez M, Linares J, de Almodovar M et al (2009). PARP inhibitors: new partners in the therapy of cancer and inflammatory diseases. Free Radic Biol Med 47, 13-26
- Nichols J, Katiyar S (2010). Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 302, 71-83
- Grant R, Braidy N, Guilleman G (2010). Polyphenol combination therapy enhances NAD+ levels and improves DNA repair after UVB damage in primary human keratinocytes [abstract]. The Australian Health & Medical Research Congress, November 2010.