Photoaging is Associated with Protein Oxidation in Human Skin In Vivo

Abstract

There is increasing evidence for the generation of reactive oxygen species in skin upon ultraviolet exposure, but little is known about their pathophysiologic relevance in human skin in vivo. We hypothesized that chronic and acute photodamage is mediated by depleted antioxidant enzyme expression and increased oxidative protein modifications. Biopsies from patients with histologically confirmed solar elastosis, from non-ultraviolet-exposed sites of age-matched controls, and from young subjects were analyzed. To evaluate the influence of acute ultraviolet exposures, buttock skin of 12 healthy subjects was irradiated repetitively on 10 d with a solar simulator and compared intraindividually to non-ultraviolet-treated contralateral sites. The antioxidant enzymes catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase were investigated by immunohistochemistry. Protein carbonyls were analyzed by immunohistochemical and immunoblotting techniques in human skin and in cell models. Whereas overall expression of antioxidant enzymes was very high in the epidermis, low baseline levels were found in the dermis. In photoaged skin, a significant depletion of antioxidant enzyme expression was observed within the stratum corneum and in the epidermis. Importantly, an accumulation of oxidatively modified proteins was found specifically within the upper dermis of photoaged skin. Upon acute ultraviolet exposure of healthy subjects, depleted catalase expression and increased protein oxidation were detected. Exposures of keratinocytes and fibroblasts to ultraviolet B, ultraviolet A, and H2O2 led to dose-dependent protein oxidation and thus confirmed in vivo results. In conclusion, the correlation between photodamage and protein oxidation was demonstrated for the first time, which hence may be a relevant pathophysiologic factor in photoaging.

The Proteasome Is an Integral Part of Solar Ultraviolet A Radiation-induced Gene Expression

“…It should be noted that it is exactly this compartment of skin which shows stromal collagen breakdown in skin aging (8). The results described in this study are the first to indicate that the presence of oxidized proteins and collagen degradation in the upper dermis of (photo)aged skin are causally linked with each other and that prevention of protein oxidation represents a potential protective strategy regarding skin aging.…”

“…One important consequence of this stress response is the increased expression of matrix metalloproteinase-1 (MMP-1), 8 which causes extracellular protein degradation and thereby contributes to photoaging of human skin. In fact, UVA-induced MMP-1 expression and the resulting increased degradation of collagen fibers, which occurs primarily in the upper part of the dermis, is thought to be a major reason for wrinkle formation in photoaged human skin (4 -6).…”

“…exactly the compartment where collagen degradation takes place, contain increased amounts of oxidized proteins (8). The functional relevance of protein oxidation in human skin is not known.…”

Tissue elasticity and the ageing elastic fibre

“…ROS generation may mediate elastic fibre damage in skin either indirectly, via protease upregulation (Yaar and Gilchrest 2007), or directly via interaction with the sulphur containing amino acids methionine and cysteine (Haenold et al 2005). The immunohistochemical identification of protein carbonyl end products in the upper dermis suggests that direct, ROS mediated, protein oxidation occurs in both acutely and chronically photoaged skin (Sander et al 2002). Finally, aberrant elastin cross-linking appears to be a feature of both photoaged and intrinsically aged skin (Jeanmaire et al 2001;Mizutari et al 1997).…”

Avaliação da eficácia fotoprotetora, penetração cutânea e segurança de formulações cosméticas contendo extratos de chá verde e 'Ginkgo biloba'

“…As EROs também estão envolvidas no processo de inflamação cutânea, em danos ao DNA (PATHAK; FITZPATRICK, 1993), em alterações nas funções celulares, bem como na depleção de sistemas de defesa enzimáticos e não-enzimáticos (PINNELL, 2003;SHINDO;WITT;PACKER, 1993), em alterações nas fibras elásticas (elastose solar) (PINNELL, 2003;RICHERT et al, 1996) e em danos em proteínas (STADMAN, 1992;SANDER, 2002;RICHERT, 1996).…”