Different Types of ROS-Scavenging Enzymes Are Expressed during Cutaneous Wound Repair

Steiling, Heike; Munz, Barbara; Werner, Sabine; Brauchle, Maria

doi:10.1006/excr.1998.4366

Cited by 153 publications

(107 citation statements)

References 37 publications

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“…These genes encode cytokines, growth factors, and their receptors, which play a role in the signaling network that orchestrates skin reconstruction in a temporally and spatially coordinated manner (21, 29 -34), proteins with a protective function, e.g. proteins that limit the amount of inflammation or oxidative stress or control bacterial infection (35)(36)(37), or extracellular matrix molecules, which erect a scaffold into which cells can grow and that can bind growth factors and other essential molecules (38).…”

Section: Discussionmentioning

confidence: 99%

The Ca2+-binding Proteins S100A8 and S100A9 Are Encoded by Novel Injury-regulated Genes

Thorey¹,

Roth²,

Regenbogen³

et al. 2001

Journal of Biological Chemistry

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218

228

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To gain insight into the molecular mechanisms underlying cutaneous wound repair, we performed a large scale screen to identify novel injury-regulated genes. Here we show a strong up-regulation of the RNA and protein levels of the two Ca 2؉ -binding proteins S100A8 and S100A9 in the hyperthickened epidermis of acute murine and human wounds and of human ulcers. Furthermore, both genes were expressed by inflammatory cells in the wound. The increased expression of S100A8 and S100A9 in wound keratinocytes is most likely related to the activated state of the keratinocytes and not secondary to the inflammation of the skin, since we also found up-regulation of S100A8 and S100A9 in the epidermis of activin-overexpressing mice, which develop a hyperproliferative and abnormally differentiated epidermis in the absence of inflammation. Furthermore, S100A8 and S100A9 expression was found to be associated with partially differentiated keratinocytes in vitro. Using confocal microscopy, both proteins were shown to be at least partially associated with the keratin cytoskeleton. In addition, cultured keratinocytes efficiently secreted the S100A8/A9 dimer. These results together with previously published data suggest that S100A8 and S100A9 are novel players in wound repair, where they might be involved in the reorganization of the keratin cytoskeleton in the wounded epidermis, in the chemoattraction of inflammatory cells, and/or in the defense against microorganisms.After cutaneous injury, a series of biological events takes place that aims at the reconstruction of the damaged skin. Among them are the migration, proliferation, and differentiation of inflammatory, epithelial, and mesenchymal cells. These cells exert specific functions in a temporally and spatially coordinated manner such as the removal of irreversibly destructed tissue, the deposition of new extracellular matrix, and the reestablishment of the cutaneous barrier (1, 2). These processes are well described at the histological level, but little is known about their molecular basis.To gain insight into the molecular mechanisms that underlie the repair process, we performed a large scale subtractive hybridization screen to systematically identify genes that are differentially expressed in injured compared with normal skin. To minimize the risk of detecting differences in gene expression levels due to changes in cellular composition rather than to transcriptional regulation, we compared normal skin with early (24 h) wounds, because only minor changes in cell type composition occur during the initial wound healing period.One of the cDNA clones that we obtained encodes the murine S100A8 protein (also known as calgranulin A, MRP8, leukocyte protein L1, or cytokine CP-10). S100 proteins are intracellular Ca 2ϩ -binding and Ca 2ϩ -modulated proteins that form antiparallel noncovalently linked dimers in solution and play a role in various Ca 2ϩ -mediated cellular functions including cell growth and differentiation, energy metabolism, cytoskeletalmembrane interactions; some of th...

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Section: Discussionmentioning

confidence: 99%

The Ca2+-binding Proteins S100A8 and S100A9 Are Encoded by Novel Injury-regulated Genes

Thorey¹,

Roth²,

Regenbogen³

et al. 2001

Journal of Biological Chemistry

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218

228

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“…The body mechanisms used in removing deleterious effects of oxidation include small antioxidant molecules like ascorbate, polyunsaturated fatty acids or sugars (mainly mannitol). Some endogenous ROS-scavenging enzymes, such as superoxide dismutases (SOD), catalase, and various peroxidases are also detoxifying agents (Heike-Steiling et al, 1999). The reducing power of the extracts and fractions presented in Table 5 indicated good activity against Fe 2+ which is capable of initiating the Haber-Weiss reaction to generate OH˙ from H 2 O 2 in a self-perpetuated chain reaction.…”

Section: Antioxidant and Free Radical Scavenging Assaymentioning

confidence: 99%

Polarity of extracts and fractions of four Combretum (Combretaceae) species used to treat infections and gastrointestinal disorders in southern African traditional medicine has a major effect on different relevant in vitro activities

Ahmed

McGaw

Elgorashi

et al. 2014

Journal of Ethnopharmacology

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Graphical abstractPhenolic-enriched extracts of four Combretum species namely Combretum bracteosum, Combretum padoides, Combretum vendae and Combretum woodii used in South African traditional medicine to treat various ranges diseases were evaluated against some diarrhoeal aetiologies. All the crude extracts and their fractions of varied polarities had good antimicrobial (non-polar fractions) or good antioxidant (polar fractions) activity. The crude extract of all the plant species were cytotoxic to Vero cell lines but did not lead to COX enzyme inhibition. Phenolic-enriched extractsFour Combretum species traditionally used for treating infectious and gastrointestinal complications in southern Africa In vitro assays: antioxidant, anti-inflammation, antimicrobial, cytotoxicity AbstractEthnopharmacological importance: Infections and gastrointestinal (GIT) disorders such as diarrhoea causes many problems in human health and animal production. Many Combretum species are used in traditional medicine to treat various diseases by rural people in Africa and Asia. Much of the work done to date on some species to validate their ethnopharmacological use was on the non-polar or intermediate polarity components. Many species are yet to be studied against relevant disease parameters using more polar extracts. Aims:The polar components were extracted and fractionated by solvent-solvent fractionation to yield fractions of different polarities. The activity of these fractions on different parameters that could be involved in infectious and gastrointestinal track (GIT) disorders was investigated. The cytotoxic activities of the extracts were also determined to evaluate the potential of these extracts to combat diarrhoea in production animals. Materials and Methods:Phenolic-enriched leaf extracts of Combretum bracteosum (Cob), Combretum padoides (Cop), Combretum vendae (Cov) and Combretum woodii (Cow) were obtained by extracting with a mixture of 70% acetone acidified with 1% HCl and n-hexane. The extract was sequentially treated by solvent-solvent fractionation with dichloromethane, ethyl acetate, and butanol to yield fractions with a large variation in polarity. The phenolic constituents of the extracts and fractions were determined using standard procedures. The antioxidant activities were determined using various standard methods. The minimum inhibitory concentrations (MICs) of the crude extracts and fractions against four bacterial and three fungal strains were assessed with a microplate serial dilution method.Cyclooxygenase (COX) and lipoxygenase (LOX) enzyme inhibitory assays and cytotoxicity studies against Vero cells were also carried out.Result: Some of the fractions had much higher antioxidant activity than the positive controls. The average EC 50 values of the extracts for the DPPH and ABTS antioxidant assays were 0.21-12 µg/ml (Cop), 0.25-16 µg/ml (Cov), 0.33-9.41 µg/ml (Cow) and 4.97-85 µg/ml (Cob) respectively while the mean EC 50 values for the positive controls ascorbic acid and trolox were 1.28-1.51 and 1.02-1.19 ...

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“…Other templates were described previously: murine interleukin (IL)-1␤, 25 murine fibronectin, and collagen 1␣(I), 26 murine vascular endothelial growth factor, 27 murine heme oxygenase 1 (HO-1), 28 murine glutathione peroxidase I, murine Cu/Zn superoxide dismutase (Cu/Zn-SOD), and murine Mn-SOD. 29 As a loading control, the RNA was hybridized with a probe for the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (gapdh). 30 Multiprobe RNase protection assays were performed with mCK-5b and mCD-1 template sets (BD Bioscience, Basel, Switzerland) according to the manufacturer's recommendations.…”

Section: Rna Isolation and Rnase Protection Assaymentioning

confidence: 99%

Peroxiredoxin 6 Is a Potent Cytoprotective Enzyme in the Epidermis

Kümin

Huber

Rülicke

et al. 2006

The American Journal of Pathology

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105

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Peroxiredoxin 6 is an enzyme that detoxifies hydrogen peroxide and various organic peroxides. In previous studies we found strongly increased expression of peroxiredoxin 6 in the hyperproliferative epidermis of wounded and psoriatic skin, suggesting a role of this enzyme in epidermal homeostasis. To address this question, we generated transgenic mice overexpressing peroxiredoxin 6 in the epidermis. Cultured keratinocytes from transgenic mice showed enhanced resistance to the toxicity of various agents that induce oxidative stress. However, overexpression of peroxiredoxin 6 did not affect skin morphogenesis or homeostasis. On skin injury, enhancement of wound closure was observed in aged animals. Most importantly, peroxiredoxin 6 overexpression strongly reduced the number of apoptotic cells after UVA or UVB irradiation. These findings demonstrate that peroxiredoxin 6 protects keratinocytes from cell death induced by reactive oxygen species in vitro and in vivo, suggesting that activation of this enzyme could be a novel strategy for skin protection under stress conditions.

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Different Types of ROS-Scavenging Enzymes Are Expressed during Cutaneous Wound Repair

Cited by 153 publications

References 37 publications

The Ca2+-binding Proteins S100A8 and S100A9 Are Encoded by Novel Injury-regulated Genes

The Ca2+-binding Proteins S100A8 and S100A9 Are Encoded by Novel Injury-regulated Genes

Polarity of extracts and fractions of four Combretum (Combretaceae) species used to treat infections and gastrointestinal disorders in southern African traditional medicine has a major effect on different relevant in vitro activities

Peroxiredoxin 6 Is a Potent Cytoprotective Enzyme in the Epidermis

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