The malondialdehyde-derived fluorophore DHP-lysine is a potent sensitizer of UVA-induced photooxidative stress in human skin cells

Sarah D. Lamore, Sara Azimian, David Horn, Bobbi L. Anglin, Koji Uchida, Christopher M. Cabello, Georg T Wondrak

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Light-driven electron and energy transfer involving non-DNA skin chromophores as endogenous photosensitizers induces oxidative stress in UVA-exposed human skin, a process relevant to photoaging and photocarcinogenesis. Malondialdehyde is an electrophilic dicarbonyl-species derived from membrane lipid peroxidation. Here, we present experimental evidence suggesting that the malondialdehyde-derived protein epitope dihydropyridine (DHP)-lysine is a potent endogenous UVA-photosensitizer of human skin cells. Immunohistochemical analysis revealed the abundant occurrence of malondialdehyde-derived and DHP-lysine epitopes in human skin. Using the chemically protected dihydropyridine-derivative (2S)-Boc-2-amino-6-(3,5-diformyl-4-methyl-4H-pyridin-1-yl)-hexanoic acid-t-butylester as a model of peptide-bound DHP-lysine, photodynamic inhibition of proliferation and induction of cell death were observed in human skin Hs27 fibroblasts as well as primary and HaCaT keratinocytes exposed to the combined action of UVA and DHP-lysine. DHP-lysine photosensitization induced intracellular oxidative stress, p38 MAPkinase activation, and upregulation of heme oxygenase-1 expression. Consistent with UVA-driven ROS formation from DHP-lysine, formation of superoxide, hydrogen peroxide, and singlet oxygen was detected in chemical assays, but little protection was achieved using SOD or catalase during cellular photosensitization. In contrast, inclusion of NaN3 completely abolished DHP-photosensitization. Taken together, these data demonstrate photodynamic activity of DHP-lysine and support the hypothesis that malondialdehyde-derived protein-epitopes may function as endogenous sensitizers of UVA-induced oxidative stress in human skin.

Original languageEnglish (US)
Pages (from-to)251-264
Number of pages14
JournalJournal of Photochemistry and Photobiology B: Biology
Volume101
Issue number3
DOIs
StatePublished - Dec 2 2010

Fingerprint

lysine
Malondialdehyde
Lysine
Skin
cells
Photosensitivity Disorders
Epitopes
Oxidative Stress
Photosensitizing Agents
proteins
catalase
inorganic peroxides
fibroblasts
1,4-dihydropyridine
hydrogen peroxide
Sodium Azide
death
Singlet Oxygen
Heme Oxygenase-1
chromophores

Keywords

  • DHP-lysine
  • Lipid peroxidation
  • Photosensitization
  • Skin photooxidative stress
  • UVA

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Biophysics

Cite this

The malondialdehyde-derived fluorophore DHP-lysine is a potent sensitizer of UVA-induced photooxidative stress in human skin cells. / Lamore, Sarah D.; Azimian, Sara; Horn, David; Anglin, Bobbi L.; Uchida, Koji; Cabello, Christopher M.; Wondrak, Georg T.

In: Journal of Photochemistry and Photobiology B: Biology, Vol. 101, No. 3, 02.12.2010, p. 251-264.

Research output: Contribution to journalArticle

Lamore, Sarah D. ; Azimian, Sara ; Horn, David ; Anglin, Bobbi L. ; Uchida, Koji ; Cabello, Christopher M. ; Wondrak, Georg T. / The malondialdehyde-derived fluorophore DHP-lysine is a potent sensitizer of UVA-induced photooxidative stress in human skin cells. In: Journal of Photochemistry and Photobiology B: Biology. 2010 ; Vol. 101, No. 3. pp. 251-264.
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abstract = "Light-driven electron and energy transfer involving non-DNA skin chromophores as endogenous photosensitizers induces oxidative stress in UVA-exposed human skin, a process relevant to photoaging and photocarcinogenesis. Malondialdehyde is an electrophilic dicarbonyl-species derived from membrane lipid peroxidation. Here, we present experimental evidence suggesting that the malondialdehyde-derived protein epitope dihydropyridine (DHP)-lysine is a potent endogenous UVA-photosensitizer of human skin cells. Immunohistochemical analysis revealed the abundant occurrence of malondialdehyde-derived and DHP-lysine epitopes in human skin. Using the chemically protected dihydropyridine-derivative (2S)-Boc-2-amino-6-(3,5-diformyl-4-methyl-4H-pyridin-1-yl)-hexanoic acid-t-butylester as a model of peptide-bound DHP-lysine, photodynamic inhibition of proliferation and induction of cell death were observed in human skin Hs27 fibroblasts as well as primary and HaCaT keratinocytes exposed to the combined action of UVA and DHP-lysine. DHP-lysine photosensitization induced intracellular oxidative stress, p38 MAPkinase activation, and upregulation of heme oxygenase-1 expression. Consistent with UVA-driven ROS formation from DHP-lysine, formation of superoxide, hydrogen peroxide, and singlet oxygen was detected in chemical assays, but little protection was achieved using SOD or catalase during cellular photosensitization. In contrast, inclusion of NaN3 completely abolished DHP-photosensitization. Taken together, these data demonstrate photodynamic activity of DHP-lysine and support the hypothesis that malondialdehyde-derived protein-epitopes may function as endogenous sensitizers of UVA-induced oxidative stress in human skin.",
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AU - Wondrak, Georg T

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