Singlet Oxygen Mediates the UVA-induced Generation of the Photoaging-associated Mitochondrial Common Deletion

Mutations of mitochondrial (mt) DNA accumulate during normal aging. The most frequent mutation is a 4,977-base pair deletion also called the common deletion, which is increased in photoaged skin. Oxidative stress may play a major role in the generation of large scale mtDNA deletions, but direct proo...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-05, Vol.274 (22), p.15345-15349
Main Authors: Berneburg, Mark, Grether-Beck, Susanne, Kürten, Viola, Ruzicka, Thomas, Briviba, Karlis, Sies, Helmut, Krutmann, Jean
Format: Article
Language:English
Subjects:
Cell Survival - radiation effects
Deuterium Oxide - pharmacology
DNA, Mitochondrial - genetics
Fibroblasts
Humans
Mutagenesis - drug effects
Mutation
Oxygen - metabolism
Peroxides - pharmacology
Reactive Oxygen Species - metabolism
Sequence Deletion - genetics
Singlet Oxygen
Skin Aging - genetics
Sodium Azide - pharmacology
Ultraviolet Rays
Vitamin E - pharmacology
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Summary:Mutations of mitochondrial (mt) DNA accumulate during normal aging. The most frequent mutation is a 4,977-base pair deletion also called the common deletion, which is increased in photoaged skin. Oxidative stress may play a major role in the generation of large scale mtDNA deletions, but direct proof for this has been elusive. We therefore assessed whether the common deletion can be generated in vitro through UV irradiation and whether reactive oxygen species are involved in this process. Normal human fibroblasts were repetitively exposed to sublethal doses of UVA radiation and assayed for the common deletion employing a semiquantitative polymerase chain reaction technique. There was a time/dose-dependent generation of the common deletion, attributable to the generation of singlet oxygen, since the common deletion was diminished when irradiating in the presence of singlet oxygen quenchers, but increased when enhancing singlet oxygen half-life by deuterium oxide. The induction of the common deletion by UVA irradiation was mimicked by treatment of unirradiated cells with singlet oxygen produced by the thermodecomposition of an endoperoxide. These studies provide evidence for the involvement of reactive oxygen species in the generation of aging-associated mtDNA lesions in human cells and indicate a previously unrecognized role of singlet oxygen in photoaging of human skin.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.22.15345