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

Georg T Wondrak, Myron K. Jacobson, Elaine L. Jacobson

Research output: Contribution to journalArticle

246 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)215-237
Number of pages23
JournalPhotochemical and Photobiological Sciences
Volume5
Issue number2
DOIs
StatePublished - 2006

Fingerprint

Photosensitizing Agents
Skin
proteins
photons
oxygen
photoexcitation
free radicals
upstream
chromophores
molecular structure
damage
matrices
cells
Photons
Reactive Oxygen Species
Photobiology
Skin Aging
Photosensitivity Disorders
Extracellular Matrix Proteins
Poisons

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Cell Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

Endogenous UVA-photosensitizers : Mediators of skin photodamage and novel targets for skin photoprotection. / Wondrak, Georg T; Jacobson, Myron K.; Jacobson, Elaine L.

In: Photochemical and Photobiological Sciences, Vol. 5, No. 2, 2006, p. 215-237.

Research output: Contribution to journalArticle

@article{dcff37a493434214b58e13378f72f14d,
title = "Endogenous UVA-photosensitizers: Mediators of skin photodamage and novel targets for skin photoprotection",
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.",
author = "Wondrak, {Georg T} and Jacobson, {Myron K.} and Jacobson, {Elaine L.}",
year = "2006",
doi = "10.1039/b504573h",
language = "English (US)",
volume = "5",
pages = "215--237",
journal = "Photochemical and Photobiological Sciences",
issn = "1474-905X",
publisher = "Royal Society of Chemistry",
number = "2",

}

TY - JOUR

T1 - Endogenous UVA-photosensitizers

T2 - Mediators of skin photodamage and novel targets for skin photoprotection

AU - Wondrak, Georg T

AU - Jacobson, Myron K.

AU - Jacobson, Elaine L.

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=32444433859&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32444433859&partnerID=8YFLogxK

U2 - 10.1039/b504573h

DO - 10.1039/b504573h

M3 - Article

C2 - 16465308

AN - SCOPUS:32444433859

VL - 5

SP - 215

EP - 237

JO - Photochemical and Photobiological Sciences

JF - Photochemical and Photobiological Sciences

SN - 1474-905X

IS - 2

ER -