Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dose intensity is emerging as a crucial determinant of success in cytotoxic cancer therapy; however, myelosuppression presents as one of the major complications encountered with increased dose intensity. Therefore, investigators are looking at the use of cytokine administration in combination with cytotoxic therapy to overcome this problem. Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) have been shown to be beneficial in protecting the hematopoietic system from radiation and chemotherapy. In this report, we give an overview of studies using IL-1 and TNF-alpha as protective agents and discuss possible mechanisms involved in their protective action. Mice pretreated with IL-1 and/or TNF-alpha were shown to be protected from the lethal effects of radiation and it has been suggested that the mechanism for this protection may be through the production of the antioxidant enzyme manganese superoxide dismutase. Similarly, aldehyde dehydrogenase, an enzyme important in the metabolic pathway of cyclophosphamide compounds, has been implicated as being important in the protection of hematopoietic cells from 4-hydroperoxycyclophosphamide. While IL-1 and TNF-alpha stimulate both of these enzymes, other mechanisms are probably also operative for other forms of chemotherapy, i.e. IL-1 and TNF-alpha were shown to protect hematopoietic progenitors from phenylketophosphamide, a cyclophosphamide derivative that is not metabolized by the enzyme aldehyde dehydrogenase. Furthermore, malignant as well as normal cells may possess receptors for these cytokines; therefore, IL-1 and TNF-alpha will have to be selective in their protection. They must be capable of protecting normal hematopoietic cells while rendering malignant cells susceptible to the toxic actions of the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The therapeutic potential of interleukin-1 and tumor necrosis factor on hematopoietic stem cells. 129 Sep 56

We used light microscopic immunohistochemistry to locate manganese superoxide dismutase, copper zinc superoxide dismutase, catalase, and glutathione-S-transferases in demineralized femora from rats of 4-14 weeks of age. Immunoblots confirmed the specificity of the polyclonal antibodies for the rat proteins of interest. Each of the enzymes exhibited a unique staining pattern. Copper-zinc superoxide dismutase was detected within some articular and epiphyseal chondrocytes of younger animals. Manganese superoxide dismutase was detected within some articular and epiphyseal chondrocytes, within some osteoprogenitor cells and osteoblasts, within many osteoclasts, and within some vascular smooth muscle cells. Catalase was identified within articular chondrocytes, epiphyseal chondrocytes, and osteocytes, whereas staining at the periphery of hypertrophic chondrocytes suggested extracellular and/or cell membrane-associted catalase. Glutathione-S-transferases were detected within and at the periphery of epiphyseal and articular chondrocytes and less prominently within cortical osteocytes. There were no major age-related changes in antioxidant enzyme distribution.
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PMID:Immunohistochemical identification of superoxide dismutases, catalase, and glutathione-S-transferases in rat femora. 157 Jul 63

Pretreatment or "priming" with vincristine (VcR) has been documented to radioprotect animals from whole body irradiation by accelerating recovery of hematopoietic marrow. The mechanisms underlying this phenomenon are unclear, but the marked similarities between priming with VcR and with immune stimulants such as endotoxin and glucan have led to speculation that VcR may be inducing such radioprotective immunoregulators as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The radioprotective ability of these cytokines, in turn, has been linked to an induction of the antioxidant enzyme manganese superoxide dismutase (Mn SOD). To establish whether priming with VcR is associated with induction of antioxidant enzymes, the activities of Mn SOD, copper-zinc (Cu-Zn) SOD, catalase (CAT), and glutathione peroxidase (GPX) were measured in the marrow of both LLca tumor-bearing and non-tumor-bearing mice given a priming dose of VcR. Results in non-tumor-bearing mice indicate that, similar to IL-1 and TNF administration, VcR treatment increases Mn-SOD activity, but not Cu-Zn SOD, CAT, or GPX activity. Furthermore, this increase occurs at the time VcR priming has been demonstrated previously to exhibit maximal radioprotection, suggesting that it may be contributing factor. However, VcR priming has been demonstrated to radioprotect both tumor-bearing and non-tumor-bearing animals, and no increase in Mn SOD activity (or the other enzymes monitored) was found in the tumor-bearing group. Rather, the presence of tumor significantly suppressed antioxidant enzyme activity. Collectively, the present data suggest that it is unlikely that increased antioxidant enzyme activity is directly involved in the VcR priming response.
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PMID:Marrow antioxidant enzyme activity in tumor-bearing and non-tumor-bearing mice following vincristine treatment. 199 2

1. A number of dietary sugars are known to mediate the effects of copper deficiency. The effects of lactose (compared with sucrose) and a dietary Cu deficiency on hepatic and cardiac antioxidant enzyme activities and tissue mineral element status were investigated in the rat. 2. Groups (n 6) of male weanling Wistar rats were provided ad lib. with deionized water and diets containing sucrose (580 g/kg) or sucrose and lactose (387 g/kg and 193 g/kg respectively) with either control (12.0 mg/kg) or deficient (1.5 mg/kg) quantities of Cu for 77 d. 3. Animals consuming the low-Cu diets exhibited significantly decreased tissue Cu levels (P less than 0.01), hepatic and cardiac cytochrome c oxidase (EC 1.9.3.1, CCO) activities (P less than 0.01 and P less than 0.001 respectively) and hepatic Cu-zinc superoxide dismutase (EC 1.15.1.1, CuZnSOD) activity (P less than 0.05). The low-Cu diets also significantly decreased cardiac manganese superoxide dismutase (EC 1.15.1.1, MnSOD), catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9, GSH-Px) activities (P less than 0.01, P less than 0.05 and P less than 0.001 respectively). 4. Hepatic Mn was significantly increased in both lactose-fed (P less than 0.001) and Cu-deficient (P less than 0.01) animals. These increases were unrelated to hepatic MnSOD activity. Cardiac Zn was significantly (P less than 0.01) increased in Cu-deficient animals. 5. Lactose feeding resulted in significantly increased cardiac CCO activity (P less than 0.001) but significantly decreased hepatic CuZnSOD (P less than 0.05), catalase (P less than 0.01) and GSH-Px (P less than 0.001) activities. 6. The activities of lactose dehydrogenase (EC 1.1.1.27, LDH) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PDH) were found to be significantly (P less than 0.05 and P less than 0.01 respectively) increased in Cu-deficient animals and G6PDH activity was significantly (P less than 0.01) decreased as a result of lactose consumption. 7. The observed changes in antioxidant enzyme activities associated with both Cu deficieny and lactose consumption may have important implications for the development of free radical mediated cell damage. However, no significant differences in either hepatic or cardiac levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation, were found.
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PMID:Effects of copper deficiency on hepatic and cardiac antioxidant enzyme activities in lactose- and sucrose-fed rats. 253 51

The human hepatoma cell line Hep 3B, which has the hepatitis B virus genome, shows over 80% decrease of copper/zinc superoxide dismutase activity, over 90% decrease of manganese superoxide dismutase activity, over 70% decrease of catalase activity, absence of glutathione peroxidase and glutathione S-transferase activities, over 270-fold increase of ferritin content and 25-fold increase of total iron compared to normal autopsy liver. These conditions of low antioxidant enzyme activities and iron overload are those which support the accumulation of oxygen free-radicals and DNA damage commonly considered to be carcinogenic mechanisms.
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PMID:Antioxidant systems in tumour cells: the levels of antioxidant enzymes, ferritin, and total iron in a human hepatoma cell line. 350 92

Exploratory factor analysis of reported specific activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase in normal human tissues, normal mouse tissues, vertebrate red blood cells and neoplastic human cell lines shows that the activities of copper-zinc superoxide dismutase, catalase and glutathione peroxidase in normal tissues are influenced by a single factor. Catalase activity has the highest loading and correlation with this factor, suggesting a catalase- or hydrogen peroxide-related influence. The activity of manganese superoxide dismutase is influenced by a separate factor. The activities of copper-zinc and manganese superoxide dismutases in normal tissues therefore appear to be dichotomously regulated. The activities of superoxide dismutase and glutathione peroxidase in vertebrate red blood cells are influenced by a single factor. The activity of catalase is influenced by a separate factor. The roles of glutathione peroxidase and catalase in hydrogen peroxide catabolism in red blood cells in fact differ. In neoplastic human cell lines, two bipolar factor factors appear to influence the activities of catalase and manganese superoxide dismutase, and glutathione peroxidase and copper-zinc superoxide dismutase, respectively. The factors are, however, mainly catalase and glutathione peroxidase activity factors as the loadings and correlations of manganese superoxide dismutase on the one hand and copper-zinc superoxide dismutase on the other, with the respective factors, are relatively small. Potentially low superoxide production and intrinsically low peroxidizability of tumour cell membranes underlie the peculiar variation of antioxidant enzyme activities in tumour cells. Factor analysis is proposed as a heuristic data reduction and hypothesis-creating technique for the variation of antioxidant and other functionally-linked enzyme activities in normal and pathological cells and tissues.
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PMID:Factor analysis of the activities of superoxide dismutase, catalase and glutathione peroxidase in normal tissues and neoplastic cell lines. 350 91

Neonatal, adult, and fetal rat lungs of 18, 20, and 22 d gestation from four to six litters were examined for cytochrome oxidase, glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, copper-zinc and manganese superoxide dismutase activities. All results were corrected for the contribution of enzymes in blood that contaminate homogenates. Because lung protein/DNA ratios and body water change significantly with gestational age, enzyme activities were expressed as U/mg DNA. All activities were low in d 18 lung and increased with advancing gestational age. Only catalase and copper-zinc superoxide dismutase increased activity in response to air breathing, suggesting that maturation of the antioxidant enzyme system is virtually complete before delivery. Activities of glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, and manganese superoxide dismutase were higher in neonatal than in adult lung.
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PMID:Pulmonary antioxidant enzyme maturation in the fetal and neonatal rat. I. Developmental profiles. 608 81

Differentiation-arrested monolayer lung cell cultures were developed from day 18, 20, and 22 rat fetuses and 3-day-old neonatal rats. These cultures were examined for antioxidant enzyme activity, and the values obtained were compared with previously reported in vivo activity. All cultures were catalase deficient, and activity could be restored by the addition of 0.25 microM Fe(NO3)3 X 9H2O to the culture medium. The other measured antioxidant enzymes--copper-zinc and manganese superoxide dismutase, glutathione peroxidase, and glucose 6-phosphate dehydrogenase-demonstrate gestation-dependent increases of activity in vivo that were not evident in vitro, supporting the concept of a circulating "maturation factor" during fetal life. When cultures from fetal days 20 and 22 and from neonatal day 3 lungs were challenged with 50% oxygen in the presence of serum, antioxidant enzyme activities were unchanged, and there was no evidence of cell damage as assessed by release of lactate dehydrogenase. In the absence of serum, however, fetal day 20 (but not fetal day 22 or neonatal day 3) lung cells showed evidence of cell damage and increased antioxidant enzyme activities. It is concluded that cultured immature fetal cells are more susceptible to oxygen toxicity than those derived from mature fetal or neonatal animals. This increased susceptibility cannot be explained on the basis of the reduced antioxidant enzyme activity observed in vivo.
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PMID:Differentiation-arrested rat fetal lung in primary monolayer cell culture. III. Antioxidant enzyme activity. 674 12

Upon exposure to a transient ischemia, the distal tubule of the kidney often escapes the severe damage which afflicts the proximal tubule. To ascertain whether this feature of the distal tubule is attributable to its intrinsic cellular properties, we focused on two pairs of unique tubule segments; distal versus proximal convoluted tubules in the superficial cortex and distal versus proximal straight tubules in the outer stripe of the outer medulla. These tubules were chosen because, firstly, they can be identified by morphology and immunostaining, and secondly, each pair has the same anatomical relationship to the circulation. Detailed morphometric analyses were performed six hours following unilateral transient ischemia in adult rats to semiquantitate the local tissue damage in these specific nephron segments. The architecture of the distal convoluted and straight tubules was remarkably well preserved, contrasting to the moderate to extensive necrotic changes seen in the proximal tubules. In search of the potential intrinsic cellular mechanism that underlies the observed difference, we examined the segmental distribution along the nephron of manganese superoxide dismutase gene transcripts by in situ hybridization. This antioxidant enzyme gene was expressed primarily in the distal tubules with contrastingly low levels of expression in the proximal tubules. Moreover, following ischemia-reperfusion, this distal tubule-dominant pattern was further accentuated immediately following reperfusion. The study indicates that the marked difference between the proximal and distal tubules in their susceptibility to injury in vivo is attributable to their intrinsic cellular properties, which include the local level of antioxidants.
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PMID:Strategic locus for the activation of the superoxide dismutase gene in the nephron. 753 59

Reactive oxygen species have been implicated as mediators of tissue injury in glomerular inflammation. The expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), was examined in primary cultures of rat glomerular epithelial cells (GEC) in response to inflammatory mediators. The results demonstrate that GEC respond to interleukin-1 (IL-1) and bacterial lipopolysaccharride (LPS) with an increase in MnSOD steady-state mRNA levels. The IL-1 alpha-mediated induction of MnSOD mRNA levels was both time- and dose-dependent. Maximal levels approximately 40-fold above controls, were observed at 12 hours with 2 ng/ml of IL-1 alpha. MnSOD protein levels were also markedly elevated by IL-1 alpha. The induction of MnSOD mRNA by IL-1 alpha required de novo transcription as well as some degree of protein synthesis. To elucidate the potential intracellular signal that mediates IL-1 alpha-dependent MnSOD expression, three classical signaling pathways were examined. We found no evidence that MnSOD induction by IL-1 alpha is mediated by either the cyclooxygenase or lipoxygenase pathway or via activation of protein kinase C. Based on the presence of IL-1 alpha in several forms of glomerular inflammation, the observed increase in MnSOD expression by this immunoregulatory cytokine must have an important role in the antioxidant defense of glomerular epithelial cells.
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PMID:Regulation of manganese superoxide dismutase in glomerular epithelial cells: mechanisms for interleukin 1 induction. 756 2


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