ePrints

Comparing the effects of mitochondrial targeted and localized antioxidants with cellular antioxidants in human skin cells exposed to UVA and hydrogen peroxide

Lookup NU author(s): Dr Anne Oyewole, Professor Mark Birch-MachinORCiD

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

Skin cancer and ageing is linked to an increased cellular reactive oxygen species (ROS) particularly following exposure to ultraviolet A (UVA) in sunlight. As mitochondria are the main source of cellular ROS, this study compared the protective effects of mitochondrial-targeted and -localised antioxidants (MitoQ and tiron respectively) with cellular antioxidants against oxidative stress induced (UVA and hydrogen peroxide (H₂O₂)) mitochondrial DNA (mtDNA) damage in human dermal fibroblasts. Using a long qPCR assay, tiron (EC₅₀ 10mM) was found to confer complete (100%) protection (P<0.001) against both UVA and H₂O₂-induced mtDNA damage whereas MitoQ (EC₅₀ 750nM) provided less protection (17% and 32%, respectively, P<0.05). This particular protective effect of tiron was greater than a range of cellular antioxidants investigated. The Nrf2 (Nuclear factor erythroid 2-related factor 2) signalling pathway provides cellular protection against oxidative stress. An ELISA assay for the Nrf2 target gene, heme oxygenase-1 (HO-1) and studies using Nrf2 siRNA both indicated that tiron’s mode of action was Nrf2 independent. The comet assay showed that tiron’s protective effect against H₂O₂-induced nuclear DNA damage was greater than the cellular antioxidants and MitoQ (P<0.001). This study provides a platform to investigate molecules with similar structure to tiron as potent and clinically relevant antioxidants

Publication metadata

Author(s): Oyewole A, Wilmot MC, Fowler M, Birch-Machin MA

Publication type: Article

Publication status: Published

Journal: FASEB Journal

Year: 2014

Volume: 28

Issue: 1

Pages: 485-494

Print publication date: 10/10/2013

Date deposited: 28/01/2014

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology

URL: http://dx.doi.org/10.1096/fj.13-237008

DOI: 10.1096/fj.13-237008

Notes: Mark Birch-Machin = Senior and corresponding Author and grant holder; first author is his PhD student

Altmetrics

Funding

Share