[Photoaging and infrared radiation. Novel aspects of molecular mechanisms]. / Lichtalterung und infrarote Strahlung. Aktuelle Aspekte molekularer Mechanismen.

Human skin is exposed to infrared (IR) radiation (760 nm-1 mm) from natural and artificial sources. In particular, the use of IR for cosmetic and "wellness" purposes has become increasingly popular and viewed as completely safe. However, epidemiological data and clinical observations indicate that IR radiation cannot be considered as totally innocuous to human skin. In particular, IR radiation, just as UV radiation, seems to be involved in photoaging and potentially also in photocarcinogenesis. In recent studies the molecular mechanisms involved in this process such as cellular signal transduction and gene expression have been characterised. IR radiation induces the synthesis of matrix metalloproteinase-1 via the mitogen-activated protein kinase signalling pathway. Since this mechanism is a major pathophysiologic factor in UV-induced skin ageing, its activation by IR radiation points to a role of IR in premature skin ageing and indicates the potential need for protection against unwanted IR effects.

Peroxynitrite activates the phosphoinositide 3-kinase/Akt pathway in human skin primary fibroblasts.

Peroxynitrite is a potent oxidizing and nitrating species formed in a diffusion-limited reaction between nitrogen monoxide and superoxide. It induces apoptosis through unknown mechanisms and is believed to interfere with receptor tyrosine kinase signalling through nitration of tyrosine residues. One pathway emanating from receptor tyrosine kinases is that leading to activation of the anti-apoptotic kinase Akt. In the present study we provide evidence that peroxynitrite, administered to cells using two different delivery systems, results in the dose- and time-dependent activation of Akt. Akt activation is rapid and followed by phosphorylation of glycogen synthase kinase-3, an established substrate of Akt. Akt activation is inhibited in the presence of the phosphoinositide 3-kinase (PI-3K) inhibitors wortmannin and LY294002, and by treatment with the platelet-derived growth factor (PDGF) receptor (PDGFR) inhibitor AG1295, indicating a requirement for PDGFR and PI-3K in mediating peroxynitrite-induced Akt activation. Accordingly, the PDGFR-A and PDGFR-B isoforms were shown to undergo rapid tyrosine phosphorylation on treatment with peroxynitrite. Prior exposure of cells to peroxynitrite interferes with PDGF-induced Akt phosphorylation. Our findings suggest that Akt activation occurs as an acute response to peroxynitrite treatment and could play an important role in influencing cell survival and/or alter the cellular response to other growth regulatory signals.

Activation pattern of mitogen-activated protein kinases elicited by peroxynitrite: attenuation by selenite supplementation.

Peroxynitrite is a mediator of toxicity in pathological processes in vivo and causes damage by oxidation and nitration reactions. Here, we report a differential induction of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells by peroxynitrite. For the exposure of cultured cells with peroxynitrite, we employed a newly developed infusion method. At 6.5 microM steady-state concentration, the activation of p38 MAPK was immediate, while JNK1/2 and ERK1/2 were activated 60 min and 15 min subsequent to 3 min of exposure to peroxynitrite, respectively. Protein-bound 3-nitrotyrosine was detected. When cells were grown in a medium supplemented with sodium selenite (1 microM) for 48 h, complete protection was afforded against the activation of p38 and against nitration of tyrosine residues. These data suggest a new role for peroxynitrite in activating signal transduction pathways capable of modulating gene expression. Further, the abolition of the effects of peroxynitrite by selenite supplementation suggests a protective role of selenium-containing proteins.