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.
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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. · 2.68 Impact Factor
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. · 1.23 Impact Factor
Article: Chronic actinic dermatitis[Show abstract] [Hide abstract]
ABSTRACT: Chronic actinic dermatitis is a photosensitive skin disease that most commonly affects elderly Caucasian males, but can also affect younger patients, particularly those with an atopic background. The clinical presentation is that of a recurrent dermatitis of the photo-exposed sites that can progress to a more lichenified and generalized appearance in the chronic phase. Investigation is best performed at specialist phototesting centers using monochromator phototesting and reveals broadband photosensitivity. Positive patch and/or photopatch testing to allergens is seen in approximately 75% of patients. The etiology of chronic actinic dermatitis has not yet been fully elucidated but a probable basis is that of delayed T-cell-mediated cellular hypersensitivity to an as yet unknown photo-induced antigen. The clinical treatment of chronic actinic dermatitis can be problematic and is focused around physical measures to prevent recurrent exacerbations and suppressive methods to limit the severity of such episodes. Immunosuppressants are often required and it is anticipated that future advances in molecular biology will allow the pathogenesis of the disease to be further understood, thereby facilitating more targeted treatment approaches.Expert Review of Dermatology 05/2006; 1(3):451-461.