Betacarotene supplementation protects from photoaging-associated mitochondrial DNA mutation.
Mutations of mitochondrial DNA accumulate during normal aging and can be detected at elevated levels in skin prematurely aged by chronic exposure to ultraviolet (UV) light (photoaging). In normal human fibroblasts, we have previously demonstrated that mtDNA deletions are induced by repetitive exposure to sublethal doses of UVA radiation mediated through singlet oxygen. Betacarotene is a known quencher of ROS and singlet oxygen in particular, and it is widely applied in photoprotective compounds. Therefore we investigated whether in our in vitro system, betacarotene is capable of protecting from the induction of photoaging-associated mtDNA deletions. All-E (trans) betacarotene was tested at doses from 0.25 to 3.0 microM for uptake into cells as well as its protective capacity. Assessment of cellular uptake of all-E betacarotene measured by HPLC revealed a dose dependent increase of intracellular concentrations, as well as an increase in oxidative metabolites. UVA-exposure led to a decrease of all-E-betacarotene, its Z-isomers and oxidative metabolites. Assessment of mtDNA deletions by PCR revealed reduced levels of mtDNA mutagenesis in cells coincubated with betacarotene at concentrations of 0.5 microM and higher. Taken together, these results indicate that betacarotene (i) is taken up into the cell in a dose dependent manner, (ii) interacts with UVA radiation in the cell and (iii) shows protective properties from the induction of a photoaging-associated mtDNA mutation.
Eicker
Jörg
J
Institut für Umweltmedizinische Forschung gGmbH at the Heinrich-Heine-University, Auf' m Hennekamp 40, D-40225 Düsseldorf, Germany.
Kürten
Viola
V
Wild
Susanne
S
Riss
Georges
G
Goralczyk
Regina
R
Krutmann
Jean
J
Berneburg
Mark
M
D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D016133:Polymerase Chain Reaction; D011837:Radiation-Protective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017384:Sequence Deletion / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects*; D013237:Stereoisomerism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D019207:beta Carotene / Q000493:pharmacokinetics / Q000494:pharmacology*
D004272:DNA, Mitochondrial; D011837:Radiation-Protective Agents; D019207:beta Carotene