Cellular sensitivity to oxidative stress in the photosensitivity dermatitis/actinic reticuloid syndrome.
ABSTRACT Skin fibroblasts from certain patients with the photosensitivity dermatitis/actinic reticuloid syndrome show enhanced sensitivity to ultraviolet radiation compared to normal fibroblasts. To probe further the link between oxidative damage and this disease, we have obtained a more extensive set of cell lines from patients with a severe form of the disease and examined their sensitivity towards oxidative stress by measuring cell survival following UVA radiation (330-450 nm) or hydrogen peroxide treatment (0.1-2.4 mM). The activation of the stress gene, heme oxygenase, has also been assessed by measuring the accumulation of mRNA after hydrogen peroxide treatment. Our studies have confirmed that a slight ultraviolet sensitivity is a characteristic of photosensitivity dermatitis/actinic reticuloid syndrome cell strains and we further demonstrate that these cell lines are particularly sensitive to hydrogen peroxide with up to a three- to fourfold increased sensitivity as compared to normal controls. We also show that certain ataxia telangiectasia strains that are especially sensitive to hydrogen peroxide are also slightly sensitive to ultraviolet radiation. Hydrogen peroxide induces accumulation of mRNA for the oxidant-inducible stress protein, heme oxygenase, with similar kinetics (maximum mRNA accumulation 2-4 h following treatment) and with a similar range of magnitudes in both normal (6.6-20.6 times mRNA increase over basal levels) and photosensitivity dermatitis/actinic reticuloid (2.9-12.8 times) skin cells. Because cells from photosensitivity dermatitis/actinic reticuloid patients show increased sensitivity towards oxidative stress but show no significant change in oxidant activation of the heme oxygenase gene, we propose that the defect involves a late stage of processing of oxidative damage rather than a compromised free radical scavenging system.
Full-textDOI: · Available from: Neil K Gibbs, Sep 02, 2014
Article: Actinic reticuloid.[Show abstract] [Hide abstract]
ABSTRACT: We report four cases of actinic reticuloid, including the first case ever reported in a woman. We have concluded that not all the patients are persistent light reactors and that the histologic presentation can be quite variable, in some cases extremely difficult to differentiate from a cutaneous lymphoma. Phototesting studies in incriminate the long UV and/or visible light range. The duration of the disease in these cases suggests a benign process which can be included among the cutaneous pseudomalignancies. Further cytoimmunological studies may incriminate the interaction of T-lymphocytes in the pathogenesis of the condition.International Journal of Dermatology 05/1980; 19(3):154-8. DOI:10.1111/j.1365-4362.1980.tb00285.x · 1.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Activation of expression of the heme oxygenase (HO) gene appears to be involved in a cellular defense system in mammalian cells. We now demonstrate that while HO-1 mRNA levels are strongly inducible in dermal fibroblasts they are barely inducible in human epidermal keratinocytes following oxidative stress (UVA radiation and hydrogen peroxide). Paralleling this result was the observation that HO-2 mRNA levels were low in dermal fibroblasts but were high in epidermal keratinocytes. In neither case was the HO-2 gene inducible. The expression of the two HO genes led to enzymatic activity in both types of skin cells with an approximately 2.5-fold higher level of enzymatic activity present in keratinocytes compared with fibroblasts derived from the same biopsy. In addition, ferritin levels, which have been found to be augmented via the HO-dependent release of iron from endogenous heme sources, were two- to three-fold higher in keratinocytes compared with matching fibroblasts. This higher ferritin pool would result in an enhancement of cellular iron sequestering capacity that may confer increased resistance to oxidative stress. Indeed, keratinocytes showed less UVA radiation-dependent cell membrane damage than fibroblasts. These results are consistent with the hypothesis that HO expression in human epidermis and dermis is related to cellular defense mechanisms that operate in human skin.Photochemistry and Photobiology 04/1995; 61(3):285-91. DOI:10.1111/j.1751-1097.1995.tb03973.x · 2.68 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Ultraviolet radiation, and in particular UVA (320-400 nm), induces significant oxidative stress to human skin. Ferritin and glutathione have been shown to be among the more important molecules within human skin cells providing protection against this damage, the presence of lower levels of these anti-oxidants giving rise to increased cellular sensitivity to stress. We compared endogenous levels of ferritin and glutathione in human melanoma cells with normal human skin fibroblasts and keratinocytes, also the response of melanoma cells to oxidative stress with fibroblasts and keratinocytes. Ferritin levels were heterogenous in the untreated melanoma cell lines tested and remained the same following oxidative stress (UVA radiation) or hemin treatment. Epidermal keratinocytes were unaffected, as were the melanoma cell lines, but skin fibroblasts showed dose-dependent ferritin depletion. Similar results were seen for glutathione alterations resulting from UVA radiation: melanoma cell lines and epidermal skin keratinocytes remained unchanged following UVA radiation, while skin fibroblasts showed dose-dependent depletion. Our results show that human melanoma cells have low ferritin and glutathione levels, yet are resistant to oxidative stress.International Journal of Cancer 07/1996; 67(3):430-4. DOI:10.1002/(SICI)1097-0215(19960729)67:3<430::AID-IJC19>3.0.CO;2-B · 5.01 Impact Factor