Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was conducted to explore the involvement of DNA damage in the suppression of contact hypersensitivity (CHS) by UV irradiation. The opossum, Monodelphis domestica, was used because cells of these marsupials have an enzyme that is activated by visible light (photoreactivating enzyme) and repairs ultraviolet radiation (UVR)-induced pyrimidine dimers in DNA. A single dose of 1,500 J/m2 of UVB (280-320 nm) radiation, representing 2 minimal erythema doses, was administered to the dorsal skin of opossums. This treatment prevented the opossums from developing a CHS response to dinitrofluorobenze (DNFB) applied either at the site of irradiation or an unirradiated site. In addition, this dose of UVR decreased the number of ATPase+ epidermal Langerhans cells in the dorsal epidermis to approximately 3% of that in unirradiated skin at the time of DNFB application. Treatment of the animals with wavelengths that activate the repair enzyme (320-500 nm, photoreactivating light, PRL) for 120 min immediately after UV irradiation inhibited the UVR-induced suppression of CHS almost completely. Exposure to PRL before UVR did not prevent UVR-induced suppression of CHS. PRL treatment after UV irradiation also prevented the decrease in the number of ATPase+ Langerhans cells. Measurements of lesions in DNA indicated that PRL treatment removed around 85% of the UVR-induced pyrimidine dimers. These data provide direct evidence that DNA, and most likely, the pyrimidine dimer, is the primary molecular target for the UVB-induced suppression of contact hypersensitivity to haptens applied to irradiated or unexposed skin.
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PMID:Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation. 252 40

We have measured UVB (280-320 nm)-induced DNA damage in skin of individuals with different sensitivities to UVB irradiation as measured by minimal erythema dose (MED). The DNA damage was susceptible to cleavage by Micrococcus luteus UV endonuclease, which recognizes pyrimidine dimers in DNA. An alkaline agarose gel electrophoresis method was used to quantitate the number of M. luteus UV endonuclease-sensitive sites in nonradioactive DNA from skin biopsies of 7 individuals irradiated with UVB (0-180 mJ X cm-2). The production of sites correlated well with MED (correlation coefficient = 0.78). The slope of the dose response curve for the most UVB-sensitive individual (MED = 24 mJ X cm-2) and for the least UVB-sensitive individual (MED = 146 mJ X cm-2) were 11.5 X 10(-4) and 2.6 X 10(-4) sites per 1000 bases per mJ X cm-2, respectively. The UVB-induced DNA damage was determined to be pyrimidine dimers by its susceptibility to cleavage by M. luteus UV endonuclease and its photoreactivability by Escherichia coli photoreactivating enzyme.
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PMID:Higher pyrimidine dimer yields in skin of normal humans with higher UVB sensitivity. 375 38

Strong epidemiological evidence confirms the role of sunlight in human melanoma induction. Furthermore, the frequency of melanocytic nevi is a good indicator of future development of melanoma and a short-term marker of adverse reactions to melanoma-inducing sun exposure in humans. Thus, the aim of this study was to develop and define an animal model for sunlight-induced nevi that can be used as a surrogate model for sunlight-induced melanoma. Five treatment groups of 30-40 Hartley albino guinea pigs/group were treated with topical 7,12-dimethylbenzanthracene at a dose range of 6-240 mg on the dorsum of the skin. At week 20, half of the animals in each group were given a 12-month regimen of minimal erythemal solar-simulated light, 3 times/week, increased weekly to maintain erythema. These regimes induced epidermally derived pigmented melanocytic nevi clinically and histologically similar to human nevi (junctional, compound, and dermal). S100 and HMB45 staining was also consistent with the patterns seen in human nevi. In contrast to the high-dose 7,12-dimethylbenzanthracene-treated animals (60 and 240 mg), where solar-simulated light had no effect on nevi multiplicity, those groups treated with low doses (24, 12, and 6 mg) had a significant increase in nevi multiplicity after 12 months of solar-simulated light treatment (24 mg, 0.5 nevi/animal unirradiated versus 1.4 nevi/animal irradiated, P = 0.03; 12 mg, 0.2 unirradiated versus 1.2 irradiated, P = 0.02; 6 mg, 0 unirradiated versus 1.9 irradiated, P = 0.008). UVB-induced minimal erythemal dose was unaltered after exposure to photoreactivating light, consistent with the observation of others that placental mammals lack the DNA photolyase responsible for strong photoreactivation seen in nonplacental mammals and lower metazoans. Thus, our guinea pig model has some of the essential elements required to be a robust animal model for human nevi and a surrogate model for melanoma. These nevi are augmented by solar-simulated light, are histologically similar, occupy the same level within the skin, have the same natural history as human nevi, and are produced in an animal lacking strong photoreactivation. These features are not found in any previously described small laboratory animal model.
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PMID:The augmentation of melanocytic nevi in guinea pigs by solar-simulated light: an animal model for human melanocytic nevi. 985 66

Ultraviolet-B (UVB) (290-320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiation-induced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40-45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.
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PMID:Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin. 1066 Jun 87

During evolution, placental mammals appear to have lost cyclobutane pyrimidine dimer (CPD) photolyase, an enzyme that efficiently removes UV-induced CPDs from DNA in a light-dependent manner. As a consequence, they have to rely solely on the more complex, and for this lesion less efficient, nucleotide excision repair pathway. To assess the contribution of poor repair of CPDs to various biological effects of UV, we generated mice expressing a marsupial CPD photolyase transgene. Expression from the ubiquitous beta-actin promoter allowed rapid repair of CPDs in epidermis and dermis. UV-exposed cultured dermal fibroblasts from these mice displayed superior survival when treated with photoreactivating light. Moreover, photoreactivation of CPDs in intact skin dramatically reduced acute UV effects like erythema (sunburn), hyperplasia and apoptosis. Mice expressing the photolyase from keratin 14 promoter photo reactivate CPDs in basal and early differentiating keratinocytes only. Strikingly, in these animals, the anti-apoptotic effect appears to extend to other skin compartments, suggesting the presence of intercellular apoptotic signals. Thus, providing mice with CPD photolyase significantly improves repair and uncovers the biological effects of CPD lesions.
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PMID:Enhanced repair of cyclobutane pyrimidine dimers and improved UV resistance in photolyase transgenic mice. 1219 74

The exposure of human skin to ultraviolet radiation (UVR) results in the formation of DNA photolesions that give rise to photoaging, mutations, cell death and the onset of carcinogenic events. Photolyase (EC 4.1.99.3) is a DNA repair enzyme that reverses damage caused by exposure to UVR. We sought to investigate whether addition of photolyase enhances the protection provided by a traditional sunscreen (SS), by reducing the in vivo formation of cyclobutane-type pyrimidine dimers (CPDs) and UVR-induced apoptosis in human skin. Ten volunteers (Fitzpatrick skin type II) were exposed to solar-simulated (ss) UVR at a three times minimal erythema dose for 4 consecutive days. Thirty minutes prior to each exposure, the test materials [vehicle, SS (sun protection factor 50) alone, and SS plus photolyase from Anacystis nidulans] were applied topically to three different sites. One additional site was left untreated and one received ssUVR only. Biopsy specimens were taken 72 h after the last irradiation. The amount of CPDs and the extent of apoptosis were measured by ELISA. Photolyase plus SS was superior to SS alone in reducing both the formation of CPDs and apoptotic cell death (both P<0.001). In conclusion, the addition of photolyase to a traditional SS contributes significantly to the prevention of UVR-induced DNA damage and apoptosis when applied topically to human skin.
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PMID:Reduced ultraviolet-induced DNA damage and apoptosis in human skin with topical application of a photolyase-containing DNA repair enzyme cream: clues to skin cancer prevention. 2208 36