Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopac increases tyrosinase activity and exerts cytotoxic effects in cultures of human melanoma cells. The possible role of hydrogen peroxide in these actions was examined. Catalase (100 micrograms/ml) completely reversed the cytotoxic action of 0.3 mM dopac and reduced its tyrosinase-stimulating effect by approximately one half. The results show that extracellular hydrogen peroxide is a mediator of both the tyrosinase-stimulating and cytotoxic actions of dopac. Analysis of the degradation products of melanin from dopac-treated melanoma cells after hydriodic acid (HI) hydrolysis revealed the presence of aminohydroxy-phenylacetic acid (AHPAc). This substance is obtained by HI hydrolysis of melanin formed by oxidation of cysteinyl-dopac. Thus, the presence of AHPAc indicates that dopac is transported into the melanocytes where it serves as a substrate for tyrosinase.
J Invest Dermatol 1991 Feb
PMID:Hydrogen peroxide as a mediator of dopac-induced effects on melanoma cells. 189 44

Photoradiation therapy with porphyrins and light offers an alternative approach to the management of certain types of cancer. The mechanism of tissue destruction mediated by this modality is poorly understood. In this study, epidermal microsomes incubated in vitro with Photofrin-I (Pf-I) and Photofrin-II (Pf-II) followed by exposure to radiation (approximately 400 nm) resulted in increased (180%) NADPH-supported (enzymatic) as well as ADP/iron-supported (140%) (nonenzymatic) lipid peroxidative damage as measured by malondialdehyde formation. Lipid peroxidation by Pf-I and Pf-II was found to be differentially affected by quenchers of singlet oxygen (2,5-dimethylfuran, histidine, beta-carotene, ascorbic acid, and sodium azide), superoxide anion (superoxide dismutase), and the hydroxyl radical (sodium benzoate, mannitol, and ethanol). Catalase, a quencher of hydrogen peroxide, afforded significant protection only against Pf-II-enhanced lipid peroxidative damage while it had little effect against the Pf-I-mediated reaction. Deuterium oxide, which is known to increase the half-life of singlet oxygen, was found to enhance Pf-I-mediated lipid peroxidation but produced insignificant effects upon Pf-II-mediated photosensitization. Our results indicate that Pf-I and Pf-II, which are employed for the photodynamic therapy of malignant tumors, evoke membrane damage by generating different reactive oxygen species. The Pf-I-mediated photodestruction mainly involves a type II mechanism via singlet oxygen formation, whereas Pf-II-mediated photodestruction preferentially involves a type I mechanism by generating superoxide anions and hydroxyl radicals. Our data indicate that tumor necrosis evoked by porphyrins and light is likely due to the generation of reactive oxygen species.
J Invest Dermatol 1988 May
PMID:Differential role of reactive oxygen intermediates in photofrin-I- and photofrin-II-mediated photoenhancement of lipid peroxidation in epidermal microsomal membranes. 283 56

Dithranol (0.01-1 micrograms/ml), but not the auto-oxidized form, caused a dose-related enhancement of the generation of reactive oxidants by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. At the same concentrations dithranol inhibited both PMNL migration to leukoattractants and mitogen-stimulated mononuclear leukocyte (MNL) proliferation. Catalase (50-100 units/ml) protected both PMNL migration and MNL proliferation from dithranol whilst ascorbate and cysteine (1 mM), which maintain dithranol in the biologically active reduced state, potentiated the inhibition. To establish the molecular mechanism of the pro-oxidative activity of dithranol its effects on cytosolic protein kinase C (PKC) activity were investigated. Dithranol caused a dose-related activation of PKC by apparent substitution for 1,2-diolein. These results demonstrate that dithranol, but not its auto-oxidation products, activates PKC which in turn initiates the generation of reactive oxidants by PMNL. Since reactive oxidants are immunosuppressive the therapeutic mechanisms of dithranol may be related to pro-oxidative interactions of this agent with skin phagocytes.
Br J Dermatol 1987 Oct
PMID:Dithranol mediates pro-oxidative inhibition of polymorphonuclear leukocyte migration and lymphocyte proliferation. 367 90

There has not as yet been an integrated, comprehensive study of the responses of dermis and epidermis in vivo to a wide range of ultraviolet (UV) doses, encompassing all major antioxidants and a sensitive marker of oxidative damage. We have irradiated hairless mice with simulated solar light at doses of 2, 5, 12.5, and 25 J/cm2 combined UVA and UVB (0.8 to 10 MED) and measured enzymic and non-enzymic antioxidants as well as lipid hydroperoxides in both epidermis and dermis to elucidate the response of cutaneous antioxidant defense mechanisms to UV stress. Among the nonenzymic antioxidants two different dose-response patterns were seen. Ascorbate was rapidly depleted at doses between 0 and 5 J/cm2 but was less affected between 5 and 25 J/cm2. In contrast, glutathione, ubiquinol/one, and alpha-tocopherol levels remained approximately equal to control levels between 0 and 5 J/cm2, then decreased to varying degrees from 5 to 25 J/cm2; ubiquinol was almost completely depleted, whereas alpha-tocopherol dropped only 30%. The concentration of lipid hydroperoxides increased throughout the dose range. These results may be explained partly by direct destruction of some antioxidants by UV light, partly by the separate antioxidant functions of the compounds, and partly by recycling of some antioxidants (e.g., alpha-tocopherol) at the expense of others (e.g., ubiquinol). Even at the lowest dose (0.8 MED) lipid hydroperoxide formation was observed. Among the enzymic antioxidants, superoxide dismutase activity decreased significantly (to 63.6% of initial activity for epidermis and 51.5% for dermis at 25 J), whereas activities of glutathione peroxidase and glutathione reductase decreased slightly. Catalase activity decreased dramatically at doses above 5 J (to 11.8% of initial activity in epidermis and 27.7% in dermis at 25 J). The dramatic loss of catalase is almost entirely accounted for by direct destruction by the simulated solar light, but superoxide dismutase was unaffected by direct exposure; hence its destruction must be due to indirect effects, either mediated by free radicals or other harmful species formed upon irradiation. At low doses of UV light many components of the cutaneous antioxidant system were damaged, whereas at high doses all components were damaged and some were almost completely destroyed.
J Invest Dermatol 1994 Apr
PMID:Dose-response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis. 815 Nov 22

This is the first study of antioxidants and oxidative-damage-related parameters in epidermis and dermis of the skin as a function of age. The four major antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase), hydrophilic and lipophilic antioxidants, and lipid hydroperoxides were assayed in both epidermis and dermis of young and old hairless mice. Catalase, superoxide dismutase, and glutathione reductase had similar activity levels in young and old animals. Only glutathione peroxidase from epidermis showed an activity decrease due to age. This decrease became apparent when enzyme activity was expressed per mg of total cellular protein. Hydrophilic and lipophilic antioxidants did not change as a function of age, nor did lipid hydroperoxide levels. Both the absolute level of oxidized glutathione and the ratio of oxidized to reduced glutathione were higher in dermis from old mice. These results suggest that skin aging is not accelerated in old age due to a general decrease in the antioxidant capacity of the tissue. The data are compatible, however, with the idea that continuous damage to skin tissue by free radicals occurs throughout an organism's lifetime because scavenging cannot be 100% efficient.
J Invest Dermatol 1994 Apr
PMID:Effect of age on antioxidants and molecular markers of oxidative damage in murine epidermis and dermis. 815 Nov 23

We measured enzymic and non-enzymic antioxidants in human epidermis and dermis from six healthy volunteers undergoing surgical procedures. Epidermis was separated from dermis by curettage and antioxidants were measured by high-performance liquid chromatography (HPLC) or standard spectrophotometric methods. The concentration of every antioxidant (referenced to skin wet weight) was higher in the epidermis than in the dermis. Among the enzymic antioxidants, the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase were higher in the epidermis compared to the dermis by 126, 61 and 215%, respectively. Catalase activity in particular was much higher (720%) in the epidermis. Glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase, which provide reduced nicotinamide adenine dinucleotide phosphate (NADPH), also showed higher activity in the epidermis than the dermis by 111% and 313%, respectively. Among the lipophilic antioxidants, the concentration of alpha-tocopherol was higher in the epidermis than the dermis by 90%. The concentration of ubiquinol 10 was especially higher in the epidermis, by 900%. Among the hydrophilic antioxidants, concentrations of ascorbic acid and uric acid were also higher in the epidermis than in the dermis by 425 and 488%, respectively. Reduced glutathione and total glutathione were higher in the epidermis than in the dermis by 513 and 471%. Thus the antioxidant capacity of the human epidermis is far greater than that of dermis. As the epidermis composes the outermost 10% of the skin and acts as the initial barrier to oxidant assault, it is perhaps not surprising that it has higher levels of antioxidants.
J Invest Dermatol 1994 Jan
PMID:Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. 828 4

The effects of systems generating active oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radical) on tyrosinase have been studied in cultured human melanoma cells. Tyrosinase activity was determined by measuring the quantity of 5-S-L-cysteinyl-L-dopa (5-S-CD) formed in the presence of D,L-dopa and L-cysteine. In some experiments, the enzyme protein was determined by radio immunoassay [RIA]. Exposure of cells to xanthine/xanthine oxidase or glucose/glucose oxidase resulted in a dose-related elevation of tyrosinase. Catalase, but not superoxide dismutase, prevented this increase indicating that hydrogen peroxide may be the agent responsible for the action, whereas superoxide anion is not involved. Hydroxyl radicals formed by the Haber-Weiss or Fenton type reactions were not found to produce elevation of tyrosinase. Catalase determinations showed no enzyme in the medium but a high concentration in the cells. Inhibition of intracellular catalase by 3-amino-1,2,4-triazole caused an increase in the tyrosinase level. The effects of dopac, xanthine/xanthine oxidase, and glucose/glucose oxidase all producing hydrogen peroxide, and increasing tyrosinase, were enhanced by the inhibition of catalase. It is concluded that hydrogen peroxide, formed by the systems, accounts for the elevation of tyrosinase level. When tyrosinase activities determined by 5-S-CD formation were compared to enzyme amounts found by RIA, the ratios of these values were always constant. This fact indicates that the increase in the tyrosinase activities was not due to an activation of the enzyme, but mirrored the quantities of enzyme protein present in the samples. On the basis of our findings, it is assumed that hydrogen peroxide is a regulator of tyrosinase in normal melanocytes and melanoma cells.
J Invest Dermatol 1993 Feb
PMID:Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells. 843 9

A comprehensive comparison of antioxidant defenses in the dermis and epidermis and their response to exposure to ultraviolet (UV) irradiation has not previously been attempted. In this study, enzymic and non-enzymic antioxidants in epidermis and dermis of hairless mice were compared. Enzyme activities are presented both as units/gram of skin and units/milligram of protein; arguments are presented for the superiority of skin wet weight as a reference base. Catalase, glutathione peroxidase, and glutathione reductase (units/gram of skin) were higher in epidermis than dermis by 49%, 86%, and 74%, respectively. Superoxide dismutase did not follow this pattern. Lipophilic antioxidants (alpha-tocopherol, ubiquinol 9, and ubiquinone 9) and hydrophilic antioxidants (ascorbic acid, dehydroascorbic acid, and glutathione) were 24-95% higher in epidermis than in dermis. In contrast, oxidized glutathione was 60% lower in epidermis than in dermis. Mice were irradiated with solar light to examine the response of these cutaneous layers to UV irradiation. After irradiation with 25 J/cm2 (UVA + UVB, from a solar simulator), 10 times the minimum erythemal dose, epidermal and dermal catalase and superoxide dismutase activities were greatly decreased. alpha-Tocopherol, ubiquinol 9, ubiquinone 9, ascorbic acid, dehydroascorbic acid, and reduced glutathione decreased in both epidermis and dermis by 26-93%. Oxidized glutathione showed a slight, non-significant increase. Because the reduction in total ascorbate and catalase was much more severe in epidermis than dermis, it can be concluded that UV light is more damaging to the antioxidant defenses in the epidermis than in the dermis.
J Invest Dermatol 1993 Mar
PMID:Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. 844 Sep 1

Either metal ions, H2O2, t-butyl hydroperoxide (tBHP), or cumene hydroperoxide (CHP) was added to the medium of cultured human keratinocytes, and the activities of key peroxide-metabolizing enzymes were examined in a sonicated cell supernatant from the treated cells. 200 microM Fe++ +200 microM Fe was without effect on any enzyme activity. 700 microM CHP or tBHP decreased glutathione (GSH) peroxidase activity by 90% after 5 h and by 100% at 20 h, even if the CHP or tBHP was removed from the media after 90 min. H2O2 at 700 microM caused a brief 17% decrease in activity, which was followed by complete recovery. GSH peroxidase was found to be rapidly inactivated in vitro by CHP, but the enzyme was also inactivated at 37 degrees C even in the absence of CHP. GSH prevented both types of inactivation. Consistent with this in vitro data, in vivo depletion of the GSH pool with buthionine sulfoximine led to lower levels of GSH peroxidase and increased sensitivity to peroxide-induced inactivation. Neither GSH reductase nor GSH S-transferase were inactivated by any treatment although CHP did cause a small increase in the activity of the latter, which was not due to induction. The activity of glucose-6-phosphate dehydrogenase was decreased 50% following treatment for 5 h with 700 microM CHP or tBHP, whereas H2O2 treatment caused a brief 15% decline, followed by recovery. The effects of peroxides were not altered by changing the concentration of Ca++ in the media. Catalase was unaffected by concentrations of peroxide up to 700 microM. Inhibition of catalase with aminotriazole slightly enhanced the toxicity of 700 microns H2O2. In summary, organic hydroperoxides at relatively low concentrations inactive key enzymes of the glutathione pathway, but hydrogen peroxide does not.
J Invest Dermatol 1993 Jun
PMID:Inactivation of enzymes of the glutathione antioxidant system by treatment of cultured human keratinocytes with peroxides. 849 23

The effects of ultraviolet A (UVA) radiation and reactive oxygen species (ROS), generated with a xanthine and xanthine oxidase (XOD) system, on collagen enzymatic degradation involving the matrix metalloproteinase (MMP) and its tissue inhibitor of metalloproteinase (TIMP) were investigated using cultured human dermal fibroblasts. Total RNA was isolated and subjected to Northern blot analysis using cDNA clones for human interstitial collagenase (MMP-1), 72-kDa type IV collagenase (MMP-2) and TIMP-2. UVA irradiation resulted in an increase in MMP-1 mRNA up to 2.3-fold, but did not stimulate MMP-2 or TIMP-2 mRNA expression. In contrast, ROS induced by the xanthine and XOD system resulted in a dose-related increase in the level of MMP-2 mRNA up to 2.1-fold and a decrease in the level of TIMP-2 mRNA by 49% in the same fibroblasts. Catalase, used as scavenger, essentially prevented the ROS-induced alterations in MMP-2 and TIMP-2 mRNA levels. These results suggest that ROS produced in the dermis may contribute to biological changes in the connective tissue matrix observed in photoaging skin by accelerating the MMP-2-related matrix degradation system.
Arch Dermatol Res 1996
PMID:The effects of ultraviolet A and reactive oxygen species on the mRNA expression of 72-kDa type IV collagenase and its tissue inhibitor in cultured human dermal fibroblasts. 875 Sep 33


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