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Issue 2, 2006
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Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection

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Abstract

Endogenous chromophores in human skin serve as photosensitizers involved in skin photocarcinogenesis and photoaging. Absorption of solar photons, particularly in the UVA region, induces the formation of photoexcited states of skin photosensitizers with subsequent generation of reactive oxygen species (ROS), organic free radicals and other toxic photoproducts that mediate skin photooxidative stress. The complexity of endogenous skin photosensitizers with regard to molecular structure, pathways of formation, mechanisms of action, and the diversity of relevant skin targets has hampered progress in this area of photobiology and most likely contributed to an underestimation of the importance of endogenous sensitizers in skin photodamage. Recently, UVA-fluorophores in extracellular matrix proteins formed posttranslationally as a consequence of enzymatic maturation or spontaneous chemical damage during chronological and actinic aging have been identified as an abundant source of light-driven ROS formation in skin upstream of photooxidative cellular stress. Importantly, sensitized skin cell photodamage by this bystander mechanism occurs after photoexcitation of sensitizers contained in skin structural proteins without direct cellular photon absorption thereby enhancing the potency and range of phototoxic UVA action in deeper layers of skin. The causative role of photoexcited states in skin photodamage suggests that direct molecular antagonism of photosensitization reactions using physical quenchers of photoexcited states offers a novel chemopreventive opportunity for skin photoprotection.

Graphical abstract: Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection

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Article information


Submitted
01 Apr 2005
Accepted
06 Jul 2005
First published
19 Aug 2005

Photochem. Photobiol. Sci., 2006,5, 215-237
Article type
Perspective

Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection

G. T. Wondrak, M. K. Jacobson and E. L. Jacobson, Photochem. Photobiol. Sci., 2006, 5, 215
DOI: 10.1039/B504573H

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