Singlet oxygen induces collagenase expression in human skin fibroblasts

Scharffetter‐­Kochanek, Karin; Wlaschek, Meinhard; Briviba, Karlis; Sies, Helmut

doi:10.1016/0014-5793(93)80357-z

Cited by 132 publications

(77 citation statements)

References 20 publications

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“…Evidence from several studies has indicated that photoaging and also intrinsic skin aging coincides with visible changes in the skin which are the results of collagen polymerization and degradation. These effects are also elicited by 1 O 2 , which is generated in vivo under exposure to UVA and is known to mediate the UVA-induced enhancement of MMP-1 expression in the dermal layer of the skin (54,56). In our hands exposure of up to 60 J/cm 2 of UVA irradiation changes the expression levels of MMP-1 mRNA and TIMP-1 mRNA (Fig.…”

Section: Discussionsupporting

confidence: 58%

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

Karademir

Ziaja

Breusing

et al. 2009

Journal of Biological Chemistry

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Solar ultraviolet (UV)A radiation is a well known trigger of signaling responses in human skin fibroblasts. One important consequence of this stress response is the increased expression of matrix metalloproteinase-1 (MMP-1), which causes extracellular protein degradation and thereby contributes to photoaging of human skin. In the present study we identify the proteasome as an integral part of the UVA-induced, intracellular signaling cascade in human dermal fibroblasts. UVA-induced singlet oxygen formation was accompanied by protein oxidation, the cross-linking of oxidized proteins, and an inhibition of the proteasomal system. This proteasomal inhibition subsequently led to an accumulation of c-Jun and phosphorylated c-Jun and activation of activator protein-1, i.e. transcription factors known to control MMP-1 expression. Increased transcription factor activation was also observed if the proteasome was inhibited by cross-linked proteins or lactacystin, indicating a general mechanism. Most importantly, inhibition of the proteasome was of functional relevance for UVA-induced MMP-1 expression, because overexpression of the proteasome or the protein repair enzyme methionine sulfoxide reductase prevented the UVA-induced induction of MMP-1. These studies show that an environmentally relevant stimulus can trigger a signaling pathway, which links intracellular and extracellular protein degradation. They also identify the proteasome as an integral part of the UVA stress response.Solar ultraviolet A (UVA; 320 -400 nm) radiation is a well known trigger of signaling responses in human dermal fibroblasts in vitro as well as in vivo in human skin (1-3). 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).The specific signaling steps involved in UVA radiation-induced MMP-1 expression have been extensively examined in recent years. These studies have identified UVA radiation-induced singlet oxygen formation as the initiating event (for review, see Ref. 7) that triggers a cascade of downstream steps which critically involve the activation of the transcription factor complex AP-1 and the subsequent increase in expression of MMP-1. This signaling model, however, includes a black box, because the precise signaling steps linking singlet oxygen with AP-1 activation are largely unknown.In this regard it is of interest that skin fibroblasts in the upper part of the dermis, i.e. 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. Under normal conditions oxidized proteins are being degraded by the proteas...

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Section: Discussionsupporting

confidence: 58%

“…Taking into account 1 O 2 formation after UVA irradiation (23,25,54), we tested for a role of singlet oxygen in UVAinduced proteasome inhibition employing NaN 3 as a singlet oxygen quencher. Results suggest that 1 O 2 is indeed a mediator of UVA-induced proteasome inhibition in fibroblasts (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

Karademir

Ziaja

Breusing

et al. 2009

Journal of Biological Chemistry

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“…UVA regulates the expression of various genes including heme oxygenase-1, matrix metalloproteinase-1, IL-1a/b, IL-6, intracellular adhesion molecule, STAT3, AP-1 and AP-2 (Basu- Modak and Tyrrell, 1993;Grether-Beck et al, 1996;Klotz et al, 1999;Maziere et al, 2001;Scharffetter-Kochanek et al, 1993;Wlaschek et al, 1997;Zhang et al, 2001b;Silvers and Bowden, 2002). Considerable work is currently underway to elucidate the signal transduction mechanisms that are induced by UVA.…”

Section: Introductionmentioning

confidence: 99%

The role of p38 in UVA-induced cyclooxygenase-2 expression in the human keratinocyte cell line, HaCaT

2002

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“…Studies on fibroblast or keratinocyte cultures revealed that through the generation of oxidative species (Tyrell and Keyse, 1990), UVA induces a decrease in Epidermal Growth Factor (EGF) binding (Djavaheri-Mergny et al, 1994), a modification of phospholipid metabolism (Hanson and deLeo, 1990) and lipid peroxidation (Morlie Á re et al, 1991;Moysan et al, 1995). In addition, UVA also leads to the production of extracellular degrading enzymes, stromelysin 1 and interstitial collagenase (Petersen et al, 1995;Sawamura et al, 1996;Scharffetter et al, 1991Scharffetter et al, , 1993Wlaschek et al, 1994Wlaschek et al, , 1995.…”

Section: Introductionmentioning

confidence: 99%

UVA exposure of human skin reconstructed in vitro induces apoptosis of dermal fibroblasts: subsequent connective tissue repair and implications in photoaging

1998

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The skin reconstructed in vitro has been previously shown to be a useful model to investigate the effects of UVB exposure (Bernerd and Asselineau, 1997). The present study describes the response to UVA irradiation. Major alterations were observed within the dermal compartment. Apoptosis of fibroblasts located in the superficial area of the dermal equivalent was observed as soon as 6 h after irradiation, leading to their disappearance after 48 h. This effect was obtained without major alterations of epidermal keratinocytes suggesting a differential cell type sensitivity to UVA radiations. In addition, collagenase I was secreted by dermal fibroblasts. The UVA dermal effects could be observed even after removal of the epidermis during the post irradiation period, demonstrating that they were independent of the keratinocyte response. The analysis of the tissue regeneration during the following 2 weeks revealed a connective tissue repair via fibroblasts proliferation, migration and active synthesis of extracellular matrix proteins such as fibronectin and procollagen I. This cellular recolonization of the superficial part of the dermal equivalent was due to activation of surviving fibroblasts located deeply in the dermal equivalent. The direct damage in the dermis and the subsequent connective tissue repair may contribute to the formation of UVA-induced dermal alterations.

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Singlet oxygen induces collagenase expression in human skin fibroblasts

Cited by 132 publications

References 20 publications

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

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

The role of p38 in UVA-induced cyclooxygenase-2 expression in the human keratinocyte cell line, HaCaT

UVA exposure of human skin reconstructed in vitro induces apoptosis of dermal fibroblasts: subsequent connective tissue repair and implications in photoaging

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