Enzymic and Non-Enzymic Antioxidants in Epidermis and Dermis of Human Skin

Shindo, Yasuko; Witt, E; Han, Derick; Epstein, William L.; Packer, Lester

doi:10.1111/1523-1747.ep12371744

Cited by 490 publications

(395 citation statements)

References 16 publications

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“…Culture in these conditions confers a protective resistance to PpIX-based photodynamic cell killing (and other oxidative stressors), which in turn could be considered an artefact of current standard cell culture conditions that contributes to a poor translation of in vitro investigations into in vivo investigations. Finally, the present experiments -by "pre-conditioning" cells under physioxiarendered the levels of antioxidant enzyme activities and redox homeostasis more akin to those observed in vivo [20,78]. We observed that, by exposing cells cultured under physioxia to temporary hyperoxia, a higher concentration of ROS was generated in a cellular environment with a lower basal redox defence, thus causing more damage to cellular components and ultimately leading to an increased treatment effect.…”

Section: Discussionmentioning

confidence: 59%

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Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Ferguson

Smerdon

Harries

et al. 2018

Free Radical Biology and Medicine

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In vivo, mammalian cells reside in an environment of 0.5-10% O 2 (depending on the tissue location within the body), whilst standard in vitro cell culture is carried out under room air. Little is known about the effects of this hyperoxic environment on treatment-induced oxidative stress, relative to a physiological oxygen environment. In the present study we investigated the effects of long-term culture under hyperoxia (air) on photodynamic treatment. Upon photodynamic irradiation, cells which had been cultured long-term under hyperoxia generated higher concentrations of mitochondrial reactive oxygen species, compared with cells in a physioxic (2% O 2 ) environment. However, there was no significant difference in viability between hyperoxic and physioxic cells. The expression of genes encoding key redox homeostasis proteins and the activity of key antioxidant enzymes was significantly higher after the long-term culture of hyperoxic cells compared with physioxic cells. The induction of antioxidant genes and increased antioxidant enzyme activity appear to contribute to the development of a phenotype that is resistant to oxidative stress-induced cellular damage and death when using standard cell culture conditions. The results from experiments using selective inhibitors suggested that the thioredoxin antioxidant system contributes to this phenotype. To avoid artefactual results, in vitro cellular responses should be studied in mammalian cells that have been cultured under physioxia. This investigation provides new insights into the effects of physioxic cell culture on a model of a clinically relevant photodynamic treatment and the associated cellular pathways.

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Section: Discussionmentioning

confidence: 59%

“…To culture cells under an atmosphere of any desired gas mixture, we implemented a technique like that which has been reported previously [20,21]. Airtight containers (Fig.…”

Section: Culture Of Cells Under Different O 2 Conditionsmentioning

confidence: 99%

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Ferguson

Smerdon

Harries

et al. 2018

Free Radical Biology and Medicine

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“…Antioxidant enzymes function cooperatively, and a change in any one of them may affect the equilibrium state of oxidative stress or the levels of reactive oxygen species (ROS). If the ROS remain, without being scavenged in the biological system, they can induce biochemical alterations, including inflammation, oxidation of lipid and protein, DNA damage and activation or inactivation of certain enzymes [38,39,[40][41][42][43]. Thus, the generation of chronic and more intense oxidative stress and inflammatory responses in the obese mice on repeated exposure to UVB irradiation would be anticipated to render them more susceptible to oxidative stress-mediated skin diseases than wild-type mice.…”

Section: Discussionmentioning

confidence: 99%

Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-κB signaling

Katiyar

Meeran

2007

Free Radical Biology and Medicine

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Obesity has been implicated in several diseases including cancer, however, the relationship of obesity and susceptibility to ultraviolet (UV) radiation-caused skin diseases has not been investigated. As UV-induced oxidative stress has been implicated in several skin diseases, we assessed the role of obesity on UVB-induced oxidative stress in genetically obese Lep ob /Lep ob (leptin-deficient) mice. Here, we report that chronic exposure to UVB (120 mJ/cm 2 ) resulted in greater oxidative stress in the skin of obese mice in terms of higher levels of H 2 O 2 and NO production, photo-oxidative damage of lipids and proteins, and greater depletion of antioxidant defense enzymes, like, glutathione, glutathione peroxidase and catalase. As UV-induced oxidative stress mediates activation of MAPK and NF-κB signaling pathways, we determined the effect of UVB on these pathways in obese mice. Exposure of obese mice to UVB resulted in phosphorylation of ERK1/2, JNK and p38 proteins of the MAPK family. Compared to wild-type mice, the obese mice exhibited higher levels of phosphorylation of these proteins, greater activation of NF-κB/p65, and higher levels of circulating proinflammatory cytokines, including TNF-α, IL-1-β and IL-6, on UVB irradiation. Together, our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVBinduced oxidative stress, and therefore may be a risk factor for skin diseases associated with UVBinduced oxidative stress.

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“…In addition, vitamin C is a major hydrophilic low-molecular weight nonenzymatic compound that belongs to a network of antioxidant defense mechanisms (22). It is known that vitamin C is widespread throughout the body, especially in the skin (24), the target organ for UV-associated cancers (22). On the other hand, riboflavin is relevant for the herein study because as an endogenous photosensitizer, this compound is ubiquitously present throughout the body, including in various highly UV-exposed organs, e.g., eye lens (21, 25).…”

mentioning

confidence: 99%

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

Besaratinia

Kim

Bates

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

102

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An increasingly popular theory ascribes UVA (>320 -400 nm) carcinogenicity to the ability of this wavelength to trigger intracellular photosensitization reactions, thereby giving rise to promutagenic oxidative DNA damage. We have tested this theory both at the genomic and nucleotide resolution level in mouse embryonic fibroblasts carrying the lambda phage cII transgene. We have also tested the hypothesis that inclusion of a cellular photosensitizer (riboflavin) can intensify UVA-induced DNA damage and mutagenesis, whereas addition of an antioxidant (vitamin C) can counteract the induced effects. Cleavage assays with formamidopyrimidine DNA glycosylase (Fpg) coupled to alkaline gel electrophoresis and ligation-mediated PCR (LM-PCR) showed that riboflavin treatment (1 M) combined with UVA1 (340 -400 nm) irradiation (7.68 J/cm 2 ) or higher dose UVA1 irradiation alone induced Fpg-sensitive sites (indicative of oxidized and/or ring-opened purines) in the overall genome and in the cII transgene, respectively. Also, the combined treatment with riboflavin and UVA1 irradiation gave rise to single-strand DNA breaks in the genome and in the cII transgene determined by terminal transferasedependent PCR (TD-PCR). A cotreatment with vitamin C (1 mM) efficiently inhibited the formation of the induced lesions. Mutagenicity analysis showed that riboflavin treatment combined with UVA1 irradiation or high-dose UVA1 irradiation alone significantly increased the relative frequency of cII mutants, both mutation spectra exhibiting significant increases in the relative frequency of G:C 3 T:A transversions, the signature mutations of oxidative DNA damage. The induction of cII mutant frequency was effectively reduced consequent to a cotreatment with vitamin C. Our findings support the notion that UVA-induced photosensitization reactions are responsible for oxidative DNA damage leading to mutagenesis. ultraviolet A radiation ͉ photosensitizer ͉ antioxidant ͉ skin cancer A large body of evidence exists regarding the association between solar UV irradiation and human skin carcinogenesis (1, 2). Sunlight UV wavelengths that reach the surface of the earth are UVA (Ͼ320-400 nm) and UVB (280-320 nm), with shorter wavelengths (UVC) being completely absorbed by stratospheric oxygen (O 2 ) (1, 3). The biologically relevant UVA and UVB have been extensively studied as the etiologic factors for skin cancer (4). The mechanistic involvement of UVB in carcinogenesis rests upon the ability of this wavelength to induce promutagenic cis-syn cyclobutane pyrimidine dimers (CPDs), pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs), and Dewar valence photoisomers (4). However, the underlying mechanism of action for UVA carcinogenicity is not fully delineated (4). Despite the weak absorbance of UVA by DNA (3), a genotoxic mode of action for UVA has been demonstrated (1). Yet, the exact process through which UVA exerts genotoxicity remains elusive (4).A widely recognized theory ascribes UVA genotoxicity to its ability to trigger intracellular photosensitizat...

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Enzymic and Non-Enzymic Antioxidants in Epidermis and Dermis of Human Skin

Cited by 490 publications

References 16 publications

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-κB signaling

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

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