Free Radicals and Dermal Damage in Photoaging and Photocarcinogenesis

  • K. Scharffetter-Kochanek
  • P. Brenneisen
  • J. Wenk
  • R. Blaudschun
  • M. Schauen
  • M. Wlaschek
Chapter
Part of the NATO Science Series book series (ASEN2, volume 55)

Abstract

The increase in UV irradiation on earth due to the stratospheric ozone depletion represents a major environmental threat to the skin increasing its risk of photooxidative damage by reactive oxygen species (ROS). ROS have been implicated in several photo dermatological disorders including photoaging. The clinical manifestations of cutaneous photoaging are due to quantitative and qualitative alterations of the dermal connective tissue. Therefore, we were interested in a better understanding of the involvement of ROS in the up-regulation of matrix metalloproteinases (MMP) responsible for connective tissue degradation in photoaging, tumor invasion and metastasis. For this purpose fibroblast monolayer cultures have been subjected to various UV modalities. In parallel fibroblasts have been challenged by distinct ROS generating systems. Using scavengers, enhancers, and inhibitors for the activity of ROS detoxifying enzymes, using stably transfected fibroblast cell lines overexpressing ROS detoxifying enzymes, and using iron chelators blocking the Fenton reaction, distinct ROS have been increased peri-or intracellularly. A time and dose dependent increase in mRNA and protein levels for collagenase was observed after exposure of fibroblasts to UV-B, UV-A, O2, H2O2, O2 -,or OH generating systems. After UV-B irradiation inhibition of the Fenton reaction using iron chelators abrogated the MMP induction substantially. Scavengers for the hydroxyl radical reduced the MMP induction after UV-B, thus pointing to the importance of the Fenton reaction and the hydroxyl radical in the UV-B response. By modulating the lifetime of O2 by enhancers and quenchers, singlet oxygen could be identified as a crucial mediator of the UV-A response. In addition, the inhibition of glutathion peroxidase, catalase and the Fenton reaction enhanced MMP mRNA induction whereas inhibition of superoxide dismutase diminished the MMP mRNA increase. Furthermore, exposure to UV-A of a stably transfected fibroblast cell line overexpressing the manganese superoxide dismutase resulted in a substantial increase in MMP mRNA. These results indicate that following UV-A irradiation, beside O2, H2O2 is mainly responsible for the induction of MMP synthesis. In conclusion, we have identified distinct ROS involved in matrix-degrading enzyme induction resulting in tissue degradation follow-ing UV irradiation. This will allow a rational risk assessment for the dermal damage of different UV modalities in photoaging and photocarcinogenesis.

Keywords

Fenton Reaction Human Dermal Fibroblast Porphyria Cutanea Tarda Indoor Tanning Interstitial Collagenase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media Dordrecht 1999

Authors and Affiliations

  • K. Scharffetter-Kochanek
    • 1
  • P. Brenneisen
    • 1
  • J. Wenk
    • 1
  • R. Blaudschun
    • 1
  • M. Schauen
    • 1
  • M. Wlaschek
    • 1
  1. 1.Department of DermatologyUniversity of CologneCologneGermany

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