Nicotinamide preferentially protects glycolysis in dermal fibroblasts under oxidative stress conditions.

Abstract

BACKGROUND Daily exposure of human skin to environmental insults such as solar radiation, pollution and smoke can lead to an elevation of oxidative stress, causing premature acceleration of skin ageing. Oxidative stress is known to disrupt cellular metabolism, which negatively impacts the skin's functionality at the cellular and tissue level. OBJECTIVES To examine the changes in cellular metabolism due to oxidative stress. METHODS Glycolysis and oxidative phosphorylation rates in human dermal fibroblasts were monitored in real time under controlled nonlethal oxidative stress conditions. Hydrogen peroxide was utilized as a surrogate stressor because numerous environmental stressors as well as intrinsic ageing trigger its production. RESULTS Hydrogen peroxide ranging between 0.5 and 3 mmol L(-1) caused a significant decrease in glycolytic and oxidative phosphorylation rates along with cellular ATP levels. Nicotinamide (NAM) was found to protect dose dependently as well as restore glycolytic rates concurrent with restoring ATP to control levels. NAM had an effective dose-response range between 0.1 and 1.0 mmol L(-1) , with maximal effects attained at 0.5 mmol L(-1) . Relative to oxidative phosphorylation, NAM was able to provide a diminished level of protection. FK866, a known NAM phosphoribosyltransferase inhibitor, was found to inhibit the protective effects of NAM significantly, suggesting part of the NAM mechanism of action involves nicotinamide adenine dinucleotide (NAD(+) ) synthesis. CONCLUSIONS These results support previous findings that NAM protects cellular metabolism from oxidative stress by preferentially affecting glycolysis. Additionally, part of its mechanism of action appears to include NAD(+) synthesis.

DOI: 10.1111/bjd.12365

Cite this paper

@article{Rovito2013NicotinamidePP, title={Nicotinamide preferentially protects glycolysis in dermal fibroblasts under oxidative stress conditions.}, author={H A Rovito and John E. Oblong}, journal={The British journal of dermatology}, year={2013}, volume={169 Suppl 2}, pages={15-24} }