H2O2 Is an Important Mediator of UVB-Induced EGF-Receptor Phosphorylation in Cultured Keratinocytes

Péus, Dominik; Vasa, R; Meves, Alexander; Pott, Markus; Beyerle, Astrid; Squillace, Karen A.; Pittelkow, Mark R.

doi:10.1046/j.1523-1747.1998.00210.x

Cited by 183 publications

(161 citation statements)

References 43 publications

(50 reference statements)

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“…The parallel receptor phosphorylation induced by irradiation with UVB and treatment with CUH, as well as the significant reduction of the UVB-triggered phosphorylation, observed after cotreatment with the antioxidant NAC, strongly imply that the UVB effect on KGFR is mediated by the intracellular generation of H 2 O 2 and ROS, as reported for EGFR (Peus et al, 1998(Peus et al, , 1999. The biochemical results obtained indicate the mechanism of H 2 O 2 generation inside the cells.…”

Section: Uvb-induced Kgfr Activation and Internalization C Marchese Ementioning

confidence: 65%

“…The earliest step in response to UV irradiation and subsequent ROS generation involves ligand-independent phosphorylation of growth factor receptors such as epidermal growth factor receptor (EGFR) (Sachsenmaier et al, 1994;Coffer et al, 1995;Huang et al, 1996;Peus et al, 1998Peus et al, , 1999, signal transduction (Sachsenmaier et al, 1994;Rosette and Karin, 1996) and rapid expression of early growth response genes (Egr-1) (Huang and Adamson, 1995).…”

Section: Introductionmentioning

confidence: 99%

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UVB-induced activation and internalization of keratinocyte growth factor receptor

et al. 2003

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Ultraviolet irradiation of mammalian cells induces several events that include activation of growth factor receptors and triggering of signal transduction pathway. Most of the UV responses are mediated by the production of reactive oxygen species (ROS) and can be blocked by antioxidants. In this study, we analysed the effect of UVB irradiation at physiologic doses and that of the prooxidant agent cumene hydroperoxide (CUH) on the activation of the receptor for keratinocyte growth factor (KGF), a key mediator of epithelial growth and differentiation. Exposure to both UVB (30-150 mJ/cm 2 ) and CUH (200 lm of NIH3T3 KGFR (KGF receptors) transfectants caused a rapid tyrosine phosphorylation and activation of KGFR similar to that induced by KGF, and internalization of the activated receptor. The KGFR expression appeared unmodified by the treatments. Ultrastructural observations of both UVB-and CUHtreated cells showed a normal morphology of the plasma membranes and intracellular organelles. The antioxidant N-acetylcysteine inhibited UVB-induced receptor phosphorylation. The generation of an intracellular oxidative stress was detected as a decrease of catalase activity and of vitamin E, and reduced glutathione levels, whereas superoxide dismutase activity was not significantly modified. A peroxidation of polyunsaturated fatty acids of cell membranes was observed after both treatments, associated with the intracellular oxidative stress. Similar biochemical events were observed on NIH3T3 untransfected control cells, suggesting that KGFR activation follows intracellular generation of ROS and is not associated with a scavenging effect. Taken together our results demonstrate that exposure to UVB and to oxidant stimuli induces a rapid intracellular production of ROS, which in turn are capable of triggering KGFR activation and internalization, similar to those induced by KGF.

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Section: Uvb-induced Kgfr Activation and Internalization C Marchese Ementioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

UVB-induced activation and internalization of keratinocyte growth factor receptor

et al. 2003

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“…An intact Txn system may be necessary to attenuate signaling by surface receptors. In response to ligand binding, NADPH-oxidase enzymes associated with the cytosolic aspect of growth factor receptors generate H 2 O 2 [22][23][24]26,[75][76][77][78][79][80][81][82][83]. A conserved catalytic cysteine at the active site of protein tyrosine phosphatases is oxidized by H 2 O 2 to a sulfenic acid, which further reacts with a backbone nitrogen to form a sulfenylamide [68].…”

Section: Effects On Signalingmentioning

confidence: 99%

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

Bondareva¹,

Capecchi²,

Iverson³

et al. 2007

Free Radical Biology and Medicine

102

115

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Thioredoxin reductases (Txnrd)1 maintain intracellular redox homeostasis in most organisms. Metazoans Txnrds also participate in signal transduction. Mouse embryos homozygous for a targeted null mutation of the txnrd1 gene, encoding the cytosolic thioredoxin reductase, were viable at embryonic day 8.5 (E8.5) but not at E9.5. Histology revealed that txnrd1 −/− cells were capable of proliferation and differentiation; however, mutant embryos were smaller than wild-type littermates and failed to gastrulate. In situ marker gene analyses indicated primitive streak mesoderm did not form. Microarray analyses on E7.5 txnrd −/− and txnrd +/+ littermates showed similar mRNA levels for peroxiredoxins, glutathione reductases, mitochondrial Txnrd2, and most markers of cell proliferation. Conversely, mRNAs encoding sulfiredoxin, IGF-binding protein 1, carbonyl reductase 3, glutamate cysteine ligase, glutathione S-transferases, and metallothioneins were more abundant in mutants. Many gene expression responses mirrored those in thioredoxin reductase 1-null yeast; however mice exhibited a novel response within the peroxiredoxin catalytic cycle. Thus, whereas yeast induce peroxiredoxin mRNAs in response to thioredoxin reductase disruption, mice induced sulfiredoxin mRNA. In summary, Txnrd1 was required for correct patterning of the early embryo and progression to later development. Conserved responses to Txnrd1 disruption likely allowed proliferation and limited differentiation of the mutant embryo cells.

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“…Detection of Intracellular Oxidative Stress by Flow Cytometric Analysis-Intracellular levels of peroxides were analyzed by flow cytometry using dihydrorhodamine 123 (DHR 123) as a specific fluorescent dye probe (17,20,21). To avoid direct photooxidation of the dye probe, cells were first treated with UV irradiation and sensitizer and then loaded with the indicator dye under light exclusion.…”

Section: Chemicals-3-hp and N-ethyl-3-hydroxypyridinium Bromide (Ne-mentioning

confidence: 99%

3-Hydroxypyridine Chromophores Are Endogenous Sensitizers of Photooxidative Stress in Human Skin Cells

Wondrak

Roberts

Jacobson

et al. 2004

Journal of Biological Chemistry

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Photocarcinogenesis and photoaging are established consequences of chronic exposure of human skin to solar irradiation. Accumulating evidence supports a causative involvement of UVA irradiation in skin photodamage. UVA photodamage has been attributed to photosensitization by endogenous skin chromophores leading to the formation of reactive oxygen species and organic free radicals as key mediators of cellular photooxidative stress. In this study, 3-hydroxypyridine derivatives contained in human skin have been identified as a novel class of potential endogenous photosensitizers. A structure-activity relationship study of skin cell photosensitization by endogenous pyridinium derivatives (pyridinoline, desmosine, pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5 -phosphate) and various synthetic hydroxypyridine isomers identified 3-hydroxypyridine and N-alkyl-3-hydroxypyridinium cation as minimum phototoxic chromophores sufficient to effect skin cell sensitization toward UVB and UVA, respectively. Photosensitization of cultured human skin keratinocytes (HaCaT) and fibroblasts (CF3) by endogenous and synthetic 3-hydroxypyridine derivatives led to a dose-dependent inhibition of proliferation, cell cycle arrest in G 2 /M, and induction of apoptosis, all of which were reversible by thiol antioxidant intervention. Enhancement of UVAinduced intracellular peroxide formation and p38 mitogen-activated protein kinase-dependent stress signaling suggest a photooxidative mechanism of skin cell photosensitization by 3-hydroxypyridine derivatives. 3-Hydroxypyridine derivatives were potent photosensitizers of macromolecular damage, effecting protein (RNase A) photocross-linking and peptide (melittin) photooxidation with incorporation of molecular oxygen. Based on these results, we conclude that 3-hydroxypyridine derivatives comprising a wide range of skin biomolecules, such as enzymatic collagen cross-links, B 6 vitamers, and probably advanced glycation end products in chronologically aged skin constitute a novel class of UVA photosensitizers, capable of skin photooxidative damage.Most of the solar UV energy incident on human skin is in the deeply penetrating UVA region (Ͼ95% from 320 to 400 nm).Increasing experimental evidence supports a causative involvement of UVA irradiation in photoaging and carcinogenesis of human skin by photooxidative mechanisms (1-5). In contrast to the formation of mutagenic pyrimidine-base photoproducts through direct absorption of UVB (290 -320 nm) radiation by skin cell DNA (6), UVA radiation results in little photoexcitation of DNA directly, and generation of reactive oxygen species (ROS) 1 and organic free radicals is a widely accepted mechanism of UVA-phototoxicity (reviewed in Ref. 7). The formation of ROS as mediators of photooxidative stress in UV-irradiated skin seems to be dependent on non-DNA chromophores acting as endogenous photosensitizers (2, 3,8). Photosensitization occurs as a consequence of initial formation of excited states of chromophores and their subsequent interaction with substrat...

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H2O2 Is an Important Mediator of UVB-Induced EGF-Receptor Phosphorylation in Cultured Keratinocytes

Cited by 183 publications

References 43 publications

UVB-induced activation and internalization of keratinocyte growth factor receptor

UVB-induced activation and internalization of keratinocyte growth factor receptor

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

3-Hydroxypyridine Chromophores Are Endogenous Sensitizers of Photooxidative Stress in Human Skin Cells

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