Peter Schroeder

Extrinsic skin aging can be attributed to infrared radiation, especially infrared. This chapter will summarize the current knowledge about the epidemiological evidence, molecular principles, and prevention/protection, as it concerns skin aging induced by infrared A.

FHRE-Luc is a promoter reporter construct that is widely used to assess the activity of FoxO (forkhead box, class O) transcription factors. We here demonstrate that this promoter construct responds to exposure of HepG2 human hepatoma cells to known agonists of the aryl hydrocarbon receptor (AhR), 3-methylcholanthrene, benzo(a)pyrene, and 6-formylin...

Exposure of human skin to sunlight is steadily rising. Complete protection against the detrimental effects of sun exposure requires strategies that have to include protection against all harmful wavelengths. Importantly, detrimental effects are not limited to the ultraviolet part of the solar spectrum but include near infrared as well. In order to...

Cell-membrane-dependent proliferative signal transduction activated by ultrafine carbon particles in lung epithelial cells involves the specific induction of Akt and ERK1/2 phosphorylation. Particle-induced generation of reactive oxygen species (ROS) and oxidative stress are regarded as initial molecular mechanisms leading to the induction of diver...

Infrared A (IRA) radiation (760-1440 nm) is a major component of solar radiation and, similar to UVR, causes photoaging of human skin by increasing the expression of matrix metalloproteinase-1 in human skin fibroblasts. In this study, we assessed the IRA-induced transcriptome in primary human skin fibroblasts. Microarray analysis revealed 599 IRA-r...

Human skin is increasingly exposed to sunlight. In order to achieve complete protection against the cumulative detrimental effects from sun exposure, topical strategies must shield against the range of solar wavelengths that can damage the skin. Importantly, the harm sustained by the skin is not limited to that caused by the ultraviolet (UV) portio...

Extrinsic skin aging has, for many years, been mainly attributed to ultraviolet (UV) radiation. Recently, it has become evident that other parts of the solar electromagnetic spectrum contribute as well. Among these, infrared radiation, especially Infrared A, has received increasing attention. This chapter will summarize the current knowledge about...

Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more t...

Deletions within the mitochondrial DNA (mtDNA) are thought to contribute to extrinsic skin aging. To study the translation of mtDNA deletions into functional and structural changes in the skin, we seeded human skin fibroblasts into collagen gels to generate dermal equivalents. These cells were either derived from Kearns-Sayre syndrome (KSS) patient...

The exact pathogenesis of photoaging of the skin is not yet known. Earlier, a number of molecular pathways explaining one or more characteristics of photoaged skin have been described, but a unifying mechanistic concept is still missing. Here we propose the "Defective Powerhouse Model of Premature Skin Aging", which reconciles most of the earlier c...

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...

Topoisomerase I is essential for DNA metabolism in nuclei and mitochondria. In yeast, a single topoisomerase I gene provides for both organelles. In vertebrates, topoisomerase I is divided into nuclear and mitochondrial paralogs (Top1 and Top1mt). To assess the meaning of this gene duplication, we targeted Top1 to mitochondria or Top1mt to nuclei....

Photoaging and skin damage that is caused by solar radiation is well known. We have recently learned that within the solar spectrum this damage not only results from ultraviolet (UV) radiation, but also from longer wavelengths, in particular near infrared radiation. Accordingly, infrared radiation (IR) has been shown to alter the collagen equilibri...

When it comes to skin damage, solar radiation is often regarded to be identical to ultraviolet (UV) but it includes much more. Over 90% of solar radiation is in the non-UV-range. Infrared A radiation (IRA, 760-1440 nm) accounts for around 30% of the solar energy reaching the earth's surface and exert detrimental effects on the skin. IRA alters the...

Sonnenstrahlung wird im Hinblick auf ihre negativen Auswirkungen für die Haut häufig mit UV-Strahlung gleichgesetzt, aber Sonnenstrahlung umfasst mehr als nur ultraviolette (UV-)Strahlung. Über 90% der Energie, die unsere Haut trifft, ist im Nicht-UV-Bereich. So konnte Infrarot-A-Strahlung (IRA, 760–1440nm), die für ein Drittel der solaren Strahlun...

Until now the susceptibility of human skin to detrimental effects of solar radiation (e.g. photoaging) has mostly been assigned to the type of radiation and to the skin type. We have raised the question whether the circadian rhythm plays a role in the susceptibility of human dermal fibrob-lasts (HDF) to IRA (760–1440 nm). IRA accounts for one third...

Infrared A radiation (IRA 760–1440 nm), a major component of solar radiation reaching the human skin, has been shown to alter the expression of matrixmetalloproteinase-1 (MMP-1) in human dermal fibroblasts involving retrograde mitochondrial signaling pathways. Aim of this study was to examine the gene regulatory potential of IRA beyond MMP-1, the...

Vascular diseases are associated with cellular aging, which is accompanied by telomere shortening counteracted in the nucleus by telomerase reverse transcriptase (TERT). Under conditions of oxidative stress TERT is exported from the nucleus and this export is mediated by Src-kinases via tyrosine phosphorylation of TERT. Nuclear export of TERT resul...

Infrared-A radiation (IRA; 760–1440 nm), a major component of natural sunlight, accounts for one third of the energy reaching human skin. We have shown in previous studies that IRA irradiation of human dermal fibroblasts (HDF) leads to an increase in expression of matrix metalloproteinase 1 (MMP-1) via an increase in mitochondrial reactive oxygen s...

Deletions of the mitochondrial DNA (mtDNA) are thought to contribute to extrinsic skin aging, because they are found at increased amounts in photoaged skin and are induced through chronic UV irradiation in human skin fibroblasts in vitro and in vivo. In order to study how the presence of mtDNA deletions translates into functional and structural cha...

Aged tissues contain increased levels of large-scale deletions of the mitochondrial (mt) DNA. Especially extrinsi-cally aged skin has been shown to carry a significant burden of mtDNA deletions along with several other structural and functional impairments. Until now the functional role of mtDNA mutations for functional and structural changes of ag...

Aging is one major risk factor for numerous diseases. The enzyme telomerase reverse transcriptase (TERT) plays an important role for aging and apoptosis. Previously, we demonstrated that inhibition of oxidative stress-induced Src kinase family-dependent nuclear export of TERT results in delayed replicative senescence and reduced apoptosis sensitivi...

Infrared (IR) radiation is non-ionizing, electromagnetic radiation with wavelengths between 760 nm and 1 mm, which is further divided into IRA, IRB and IRC. IR accounts for more than half of the solar energy that reaches the human skin. While IRB and IRC do not penetrate deeply into the skin, more than 65% of IRA reaches the dermis. Human skin is i...

Changes of the redox balance in cells alter the availability of intracellular free Zn(2+). Here, cells were exposed to ultraviolet (UV)-A, UV-B, or infrared (IR)-A light irradiation, and the intracellular free zinc pool was monitored. Under sublethal conditions only UV-A irradiation resulted in a transient cytoplasmic and nuclear increase of intrac...

Exposure of human skin to solar radiation, which includes ultraviolet (UV) radiation (UVA and UVB) visible light and infrared radiation, induces skin aging. The effects of light have been attributed to irradiation-induced reactive oxygen species (ROS) formation, but the specific signaling pathways are not well understood. Detrimental effects of sol...

Human skin is exposed to infrared radiation (IR) from natural and artificial sources. In previous studies, near IR radiation (IRA; 760-1,440 nm) was shown to elicit a retrograde mitochondrial signaling response leading to induction of matrix metalloproteinase-1 (MMP-1) expression. These studies, however, have exclusively employed cultured human ski...

Sunbeds have become very popular and, as a result, health effects of their use are of growing concern. In this regard, exposure to ultraviolet radiation from sunbeds may cause premature skin aging. Evidence for this assumption, however, has thus far been elusive. In this study, we assessed whether sunbed use induced the generation of a large-scale...

In photoaged skin, wrinkles result from an increased degradation and a decreased de novo synthesis of collagen fibers. At the molecular level, photoaged skin is characterized by increased amounts of large-scale deletions of the mitochondrial (mt) genome such as the 4,977 bp common deletion. The common deletion can be generated in dermal fibroblasts...

Im Jahre 1988 wurde erstmals in einer vehikelkontrollierten, doppelblinden Studie zweifelsfrei gezeigt, dass die topische Applikation von Tretinoin in der Lage ist, die mit einer Lichtalterung einhergehende Ausbildung von Hautfalten zu reduzieren. Diese klinische Beobachtung stimulierte ein großes Interesse an den pathogenetischen Mechanismen, die...

The redox regulator thioredoxin-1 (Trx) is a potent antioxidative enzyme and exerts important cellular functions. Physiological concentrations of reactive oxygen species (ROS) and of nitric oxide (NO) act as second messengers. Previously, we demonstrated that ROS and NO reduced apoptosis in a Trx-dependent manner. The aim of this study was to deter...

Infrared A radiation (IRA) is a major component of sunlight. Similar to ultraviolet (UV) B and UVA, IRA induces gene transcription. In contrast to the UV response very little is known about the IRA response. In the present study, IRA-induced expression of matrix metalloproteinase-1 (MMP-1) was found to be mediated by the formation of intracellular...

Environmental factors, including sunlight, are able to induce severe oxidative protein damage. The modified proteins are either repaired, degraded or escape from degradation and aggregate. In the present study we tested the effect of different sunlight components such as UV-A, UV-B, and infrared radiation on protein oxidation in vitro. We chose gly...

UVB radiation-induced signaling in mammalian cells involves two major pathways: one that is initiated through the generation of DNA photoproducts in the nucleus and a second one that occurs independently of DNA damage and is characterized by cell surface receptor activation. The chromophore for the latter one has been unknown. Here, we report that...

The integrity of the mitochondrial genome is of crucial importance for the cellular energy metabolism, and increased mutation rates are causally related to premature ageing. We demonstrate that replacement of normal deionized water with processed water in cell culture medium decreases the constitutive levels of the most frequent large-scale deletio...

In the recent years, molecular research has successfully elucidated some of the major mechanisms through which environmental noxae damage human skin. From this knowledge, novel concepts for skin protection have been developed. Here, we provide a brief overview of some of the most exciting and intriguing concepts in molecular dermatotoxicology.

Oxidative damage accumulation in macromolecules has been considered as a cause of cellular damage and pathology. Rarely, the oxidative stress parameters in healthy humans related to the individual age have been reported. The purpose of this study was to examine the redox status in plasma and erythrocytes of healthy individuals and determine correla...

As skin physiology and skin aging are very complex processes, it is not surprising that ongoing research efforts uncover more and more noxious substances with detrimental effects on the skin. Expanding the field of view, the effects of IR radiation, tobacco smoke, and ozone have received increasing attention. Besides the understanding of the pathom...

Mutations of mitochondrial (mt) DNA play a role in neurodegeneration, normal aging, premature aging of the skin (photoaging), and tumors. We and others could demonstrate that mtDNA mutations can be induced in skin cells in vitro and in normal human skin in vivo by repetitive, sublethal ultraviolet (UV)-A-irradiation. These mutations are mediated by...

The flavonoid (-)-epicatechin was previously demonstrated to interfere with tyrosine nitration by peroxynitrite [Biochem. Biophys. Res. Commun. 285 (2001) 782]. This effect was hypothesized to be based upon an interaction of epicatechin with a transiently generated tyrosyl radical. In the present study, using electron paramagnetic resonance, we dem...

Low molecular weight antioxidants are an important part of the antioxidative defense mechanisms of cells and organisms. This chapter gives a short overview of the actions of the main antioxidants, including uric acid, ubichinones, lipoic acid, vitamins C and E, carotenoids, and phenolic compounds. The antioxidative properties of these endogeous and...

Environmental factors are known sources for oxidative stress. In consequence of the numerous influences that define our environment, environmental oxidative stress can derive from several sources. Such sources can be categorised with respect to their mechanisms of action: Where are the reactive oxygen species generated? Where do they take effect? A...

Nitrite occurs ubiquitously in biological fluids such as blood and sweat, representing an oxidation product of nitric oxide. Nitrite has been associated with a variety of adverse effects such as mutagenicity, carcinogenesis, and toxicity. In contrast, here we demonstrate that the presence of nitrite, but not nitrate, during irradiation of endotheli...

Human skin is exposed to infrared (IR) radiation (760 nm-1 mm) from natural as well as artificial sources that are increasingly used for cosmetic or medical purposes. Epidemiological data and clinical observations, however, indicate that IR radiation cannot be considered as totally innocuous to human skin. In particular, IR radiation, similar to ul...

The dietary flavanol (-)-epicatechin protects against nitration and oxidation reactions of the inflammatory mediator peroxynitrite in hydrophilic and hydrophobic environments. Bioavailability and cellular uptake of (-)-epicatechin are not yet fully characterized. Here, the octanol/buffer partition coefficient of (-)-epicatechin is observed to be 1....

Cardiopulmonary bypass induces a generalized inflammatory reaction accompanied by free radical generation. Depletion of antioxidants could result and is reported for vitamin E and C. We investigated the effect of cardiopulmonary bypass on plasma concentrations of alpha-tocopherol, retinol, and biochemical variables (e.g., triacylglycerol, cholester...

Peroxynitrite, generated for example in inflammatory processes, is capable of nitrating and oxidizing biomolecules, implying a considerable impact on the integrity of cellular structures. Cells respond to stressful conditions by the activation of signaling pathways, including receptor tyrosine kinase-dependent pathways such as mitogen-activated pro...

The flavanol (−)-epicatechin is known to protect against peroxynitrite-induced nitration and oxidation reactions. This study investigated the protection afforded by (−)-epicatechin against both these reaction types on one target molecule, the aminoacid tyrosine, in a hydrophilic milieu as well as with a lipophilic tyrosine derivative, N-t-BOC -tyro...

The flavanol (−)-epicatechin has been found to protect against damage inflicted by peroxynitrite, an inflammatory intermediate. Here, epicatechin was tested in systems of increasing complexity. The compound efficiently protected against nitration of protein tyrosine residues by peroxynitrite (IC50 ≈ 0.02 mol epicatechin/mol peroxynitrite). However,...

Peroxynitrite is a mediator molecule in inflammation, and its biological properties are being studied extensively. Flavonoids, which are natural plant constituents, protect against peroxynitrite and thereby could play an anti-inflammatory role. Procyanidin oligomers of different sizes (monomer through nonamer), isolated from the seeds of Theobroma...

Der Entzündungsmediator Peroxynitrit wird im Organismus aus Stickstoffmonoxid und Superoxidradikalanionen gebildet und dient der Abwehr eindringender Mikro-organismen, basierend auf seiner stark oxidierenden und nitrierenden Wirkung, die z.B. zur Modifikation von Proteinen und Nukleinsäuren führt. Doch auch körperei-gene Zellen im entzündeten Geweb...