3-Hydroxypyridine chromophores are endogenous sensitizers of photooxidative stress in human skin cells

Georg T Wondrak, Michael J. Roberts, Myron K. Jacobson, Elaine L. Jacobson

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Photocarcinogenesis and photoaging are established consequences of chronic exposure of human skin to solar irradiation. Accumulating evidence supports a causative involvement of UVA irradiation in skin photo-damage. UVA photodamage has been attributed to photosensitization by endogenous skin chromophores leading to the formation of reactive oxygen species and organic free radicals as key mediators of cellular photooxidative stress. In this study, 3-hydroxypyridine derivatives contained in human skin have been identified as a novel class of potential endogenous photosensitizers. A structure-activity relationship study of skin cell photosensitization by endogenous pyridinium derivatives (pyridinoline, desmosine, pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5′-phosphate) and various synthetic hydroxypyridine isomers identified 3-hydroxypyridine and N-alkyl-3-hydroxypyridinium cation as minimum phototoxic chromophores sufficient to effect skin cell sensitization toward UVB and UVA, respectively. Photosensitization of cultured human skin keratinocytes (HaCaT) and fibroblasts (CF3) by endogenous and synthetic 3-hydroxypyridine derivatives led to a dose-dependent inhibition of proliferation, cell cycle arrest in G2/M, and induction of apoptosis, all of which were reversible by thiol antioxidant intervention. Enhancement of UVA-induced intracellular peroxide formation and p38 mitogen-activated protein kinase-dependent stress signaling suggest a photooxidative mechanism of skin cell photosensitization by 3-hydroxypyridine derivatives. 3-Hydroxypyridine derivatives were potent photosensitizers of macromolecular damage, effecting protein (RNase A) photocross-linking and peptide (melittin) photooxidation with incorporation of molecular oxygen. Based on these results, we conclude that 3-hydroxypyridine derivatives comprising a wide range of skin biomolecules, such as enzymatic collagen cross-links, B6 vitamers, and probably advanced glycation end products in chronologically aged skin constitute a novel class of UVA photosensitizers, capable of skin photooxidative damage.

Original languageEnglish (US)
Pages (from-to)30009-30020
Number of pages12
JournalJournal of Biological Chemistry
Volume279
Issue number29
DOIs
StatePublished - Jul 16 2004

Fingerprint

Chromophores
Skin
Photosensitivity Disorders
Derivatives
Photosensitizing Agents
Desmosine
Pyridoxamine
3-hydroxypyridine
Irradiation
Pyridoxal
Melitten
G2 Phase Cell Cycle Checkpoints
Pancreatic Ribonuclease
Pyridoxine
Skin effect
Advanced Glycosylation End Products
Pyridoxal Phosphate
Photooxidation
Molecular oxygen
Peroxides

ASJC Scopus subject areas

  • Biochemistry

Cite this

3-Hydroxypyridine chromophores are endogenous sensitizers of photooxidative stress in human skin cells. / Wondrak, Georg T; Roberts, Michael J.; Jacobson, Myron K.; Jacobson, Elaine L.

In: Journal of Biological Chemistry, Vol. 279, No. 29, 16.07.2004, p. 30009-30020.

Research output: Contribution to journalArticle

Wondrak, Georg T ; Roberts, Michael J. ; Jacobson, Myron K. ; Jacobson, Elaine L. / 3-Hydroxypyridine chromophores are endogenous sensitizers of photooxidative stress in human skin cells. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 29. pp. 30009-30020.
@article{f902360883af47d0b19deeb12a29a105,
title = "3-Hydroxypyridine chromophores are endogenous sensitizers of photooxidative stress in human skin cells",
abstract = "Photocarcinogenesis and photoaging are established consequences of chronic exposure of human skin to solar irradiation. Accumulating evidence supports a causative involvement of UVA irradiation in skin photo-damage. UVA photodamage has been attributed to photosensitization by endogenous skin chromophores leading to the formation of reactive oxygen species and organic free radicals as key mediators of cellular photooxidative stress. In this study, 3-hydroxypyridine derivatives contained in human skin have been identified as a novel class of potential endogenous photosensitizers. A structure-activity relationship study of skin cell photosensitization by endogenous pyridinium derivatives (pyridinoline, desmosine, pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5′-phosphate) and various synthetic hydroxypyridine isomers identified 3-hydroxypyridine and N-alkyl-3-hydroxypyridinium cation as minimum phototoxic chromophores sufficient to effect skin cell sensitization toward UVB and UVA, respectively. Photosensitization of cultured human skin keratinocytes (HaCaT) and fibroblasts (CF3) by endogenous and synthetic 3-hydroxypyridine derivatives led to a dose-dependent inhibition of proliferation, cell cycle arrest in G2/M, and induction of apoptosis, all of which were reversible by thiol antioxidant intervention. Enhancement of UVA-induced intracellular peroxide formation and p38 mitogen-activated protein kinase-dependent stress signaling suggest a photooxidative mechanism of skin cell photosensitization by 3-hydroxypyridine derivatives. 3-Hydroxypyridine derivatives were potent photosensitizers of macromolecular damage, effecting protein (RNase A) photocross-linking and peptide (melittin) photooxidation with incorporation of molecular oxygen. Based on these results, we conclude that 3-hydroxypyridine derivatives comprising a wide range of skin biomolecules, such as enzymatic collagen cross-links, B6 vitamers, and probably advanced glycation end products in chronologically aged skin constitute a novel class of UVA photosensitizers, capable of skin photooxidative damage.",
author = "Wondrak, {Georg T} and Roberts, {Michael J.} and Jacobson, {Myron K.} and Jacobson, {Elaine L.}",
year = "2004",
month = "7",
day = "16",
doi = "10.1074/jbc.M404379200",
language = "English (US)",
volume = "279",
pages = "30009--30020",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "29",

}

TY - JOUR

T1 - 3-Hydroxypyridine chromophores are endogenous sensitizers of photooxidative stress in human skin cells

AU - Wondrak, Georg T

AU - Roberts, Michael J.

AU - Jacobson, Myron K.

AU - Jacobson, Elaine L.

PY - 2004/7/16

Y1 - 2004/7/16

N2 - Photocarcinogenesis and photoaging are established consequences of chronic exposure of human skin to solar irradiation. Accumulating evidence supports a causative involvement of UVA irradiation in skin photo-damage. UVA photodamage has been attributed to photosensitization by endogenous skin chromophores leading to the formation of reactive oxygen species and organic free radicals as key mediators of cellular photooxidative stress. In this study, 3-hydroxypyridine derivatives contained in human skin have been identified as a novel class of potential endogenous photosensitizers. A structure-activity relationship study of skin cell photosensitization by endogenous pyridinium derivatives (pyridinoline, desmosine, pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5′-phosphate) and various synthetic hydroxypyridine isomers identified 3-hydroxypyridine and N-alkyl-3-hydroxypyridinium cation as minimum phototoxic chromophores sufficient to effect skin cell sensitization toward UVB and UVA, respectively. Photosensitization of cultured human skin keratinocytes (HaCaT) and fibroblasts (CF3) by endogenous and synthetic 3-hydroxypyridine derivatives led to a dose-dependent inhibition of proliferation, cell cycle arrest in G2/M, and induction of apoptosis, all of which were reversible by thiol antioxidant intervention. Enhancement of UVA-induced intracellular peroxide formation and p38 mitogen-activated protein kinase-dependent stress signaling suggest a photooxidative mechanism of skin cell photosensitization by 3-hydroxypyridine derivatives. 3-Hydroxypyridine derivatives were potent photosensitizers of macromolecular damage, effecting protein (RNase A) photocross-linking and peptide (melittin) photooxidation with incorporation of molecular oxygen. Based on these results, we conclude that 3-hydroxypyridine derivatives comprising a wide range of skin biomolecules, such as enzymatic collagen cross-links, B6 vitamers, and probably advanced glycation end products in chronologically aged skin constitute a novel class of UVA photosensitizers, capable of skin photooxidative damage.

AB - Photocarcinogenesis and photoaging are established consequences of chronic exposure of human skin to solar irradiation. Accumulating evidence supports a causative involvement of UVA irradiation in skin photo-damage. UVA photodamage has been attributed to photosensitization by endogenous skin chromophores leading to the formation of reactive oxygen species and organic free radicals as key mediators of cellular photooxidative stress. In this study, 3-hydroxypyridine derivatives contained in human skin have been identified as a novel class of potential endogenous photosensitizers. A structure-activity relationship study of skin cell photosensitization by endogenous pyridinium derivatives (pyridinoline, desmosine, pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5′-phosphate) and various synthetic hydroxypyridine isomers identified 3-hydroxypyridine and N-alkyl-3-hydroxypyridinium cation as minimum phototoxic chromophores sufficient to effect skin cell sensitization toward UVB and UVA, respectively. Photosensitization of cultured human skin keratinocytes (HaCaT) and fibroblasts (CF3) by endogenous and synthetic 3-hydroxypyridine derivatives led to a dose-dependent inhibition of proliferation, cell cycle arrest in G2/M, and induction of apoptosis, all of which were reversible by thiol antioxidant intervention. Enhancement of UVA-induced intracellular peroxide formation and p38 mitogen-activated protein kinase-dependent stress signaling suggest a photooxidative mechanism of skin cell photosensitization by 3-hydroxypyridine derivatives. 3-Hydroxypyridine derivatives were potent photosensitizers of macromolecular damage, effecting protein (RNase A) photocross-linking and peptide (melittin) photooxidation with incorporation of molecular oxygen. Based on these results, we conclude that 3-hydroxypyridine derivatives comprising a wide range of skin biomolecules, such as enzymatic collagen cross-links, B6 vitamers, and probably advanced glycation end products in chronologically aged skin constitute a novel class of UVA photosensitizers, capable of skin photooxidative damage.

UR - http://www.scopus.com/inward/record.url?scp=3142718195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3142718195&partnerID=8YFLogxK

U2 - 10.1074/jbc.M404379200

DO - 10.1074/jbc.M404379200

M3 - Article

C2 - 15133022

AN - SCOPUS:3142718195

VL - 279

SP - 30009

EP - 30020

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

ER -