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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-Machin

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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


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