Elastin Modification by 4-Hydroxynonenal in Hairless Mice Exposed to UV-A. Role in Photoaging and Actinic Elastosis.
Chronic exposure to ultraviolet (UV) radiation causes oxidative stress, which is involved in photoaging and actinic elastosis. UV and reactive oxygen species generate lipid peroxidation products, including the α, β-unsaturated carbonyl compounds such as acrolein or 4-hydroxynonenal (4-HNE). These aldehydes can modify proteins of the extracellular matrix, but their role in the pathogenesis of photoaging is not clarified. The aim of this study was to investigate whether these aldehydes contribute to alter elastin metabolism and whether topical carbonyl scavengers delay UV-induced skin photoaging. Hairless mice (4-6-week old) daily exposed to UV-A (20 J cm(-2) per day, up to 600 J cm(-2)) exhibited the typical features of photoaging, associated with a significant increase in 4-HNE- and acrolein-adduct content, and elastotic material deposition. Immunofluorescence studies showed the accumulation of 4-HNE adducts on elastin in the dermis of UV-A-exposed mice. This was mimicked in vitro by incubating orcein-elastin with 4-HNE or acrolein, which altered its digestion by leukocyte-elastase, a feature possibly involved in the accumulation of elastotic material. A daily topical application of carnosine completely reversed the development of photoaging alterations and 4-HNE-adduct formation on elastin. These data emphasize the role of 4-HNE and acrolein in the mechanism of photoaging, and the preventive effect of carbonyl scavengers.
Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
Pauline
P
Larroque-Cardoso
Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
Caroline
C
Camaré
Centre Européen de Recherche sur la Peau, Pierre Fabre Company, Toulouse, France.
Florence
F
Nadal-Wollbold
University of Toulouse, Toulouse, France.
Marie-Hélène
MH
Grazide
Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
Mélanie
M
Pucelle
Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
Sandra
S
Garoby-Salom
Centre Européen de Recherche sur la Peau, Pierre Fabre Company, Toulouse, France.
Patrick
P
Bogdanowicz
Centre Européen de Recherche sur la Peau, Pierre Fabre Company, Toulouse, France.
Gwendal
G
Josse
Centre Européen de Recherche sur la Peau, Pierre Fabre Company, Toulouse, France.
Anne-Marie
AM
Schmitt
School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
Koji
K
Uchida
Division of Pathology, Clinical Hospital Centre, Zagreb, Croatia.
Kamelija
K
Zarkovic
Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
Robert
R
Salvayre
Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France. Electronic address: anne.negre-salvayre@inserm.fr.
Anne
A
Nègre-Salvayre
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002336:Carnosine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004548:Elasticity / Q000187:drug effects / Q000502:physiology; D004549:Elastin / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008812:Mice, Hairless; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010787:Photosensitivity Disorders / Q000188:drug therapy* / Q000378:metabolism*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D015595:Skin Aging / Q000187:drug effects* / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000447:Aldehydes; D002336:Carnosine; D004549:Elastin; C027576:4-hydroxy-2-nonenal