Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Random screening of an Onchocerca volvulus third-stage (L3) cDNA library identified a highly abundant cDNA encoding a newly discovered antioxidant enzyme, thioredoxin peroxidase (TPx), a member of the peroxidoxin superfamily. This TPx cDNA (Ov-tpx-2) encodes a polypeptide of 199 amino acid residues with a calculated molecular weight of 21,890 Da. The Ov-tpx-2 cDNA represents roughly 2.5% of the total cDNAs from the L3 cDNA library. The gene was expressed in Escherichia coli and the protein product was shown to have antioxidant activity. Antiserum raised against Ov-TPX-2 recognized a native protein from extracts of both the L3 and adult-stages with a molecular weight of 22 kD. The localization and stage-specificity of Ov-TPX-2 protein was analyzed by immunocytochemistry and immunoelectron microscopy using monospecific antibodies. Expression was detected in late first-stage larvae during development in the vector and increased in intensity during differentiation to the infective L3-stage. The antigen was also detected in post-infective larvae and adult worms. In larvae, Ov-TPX-2 protein was predominantly localized to the hypodermis and cuticle, with additional sites in the hypodermal chords and multivesicular bodies. In adult worms, the primary sites of expression were the uterine epithelium and intestine, with additional labeling of the body wall and cuticle. Developing embryos and microfilariae in utero were bathed in Ov-TPX-2 protein discharged from epithelial cells. These results suggest that Ov-TPX-2 may protect the parasites from being damaged by host-generated oxidative stress and that Ov-TPX-2 protein provides the H2O2-detoxifying activity predicted but not previously identified in filarial parasites. Its highly upregulated expression in infective larvae may aid in parasite establishment following transmission to the definitive host.
Mol Biochem Parasitol 1998 Mar 15
PMID:Thioredoxin peroxidase from Onchocerca volvulus: a major hydrogen peroxide detoxifying enzyme in filarial parasites. 956 16

The effects of Vitamin E administration on antioxidant enzyme activities and nitrite-nitrate levels of the reperfused rat kidney tissues were investigated by performing a 60 min ischemia followed by 24 and 72 hours of reperfusion. Vitamin E administration or the placebo (SF) was applied as 100 mg/kg BW. As expected, catalase (CAT) (p<0.05) and superoxide dismutase (SOD) (p<0.05) activities of ischemia/reperfused (I/R) kidney tissue were lower and malondialdehyde (MDA) levels were higher than control kidneys in both SF and vitamin E treated groups following 24 h reperfusion. During reperfusion of long term (72 h), vitamin E triggered a decrease in the MDA levels in the ischemic tissue, while it did not provoke a significant effect on SOD and catalase activities. Total nitrite levels of ischemic tissues in both of the groups were higher than matched control kidneys and this elevation was more clear in the vitamin E treated group. Our results showed that vitamin E has a protective effect on I/R injury, by a direct chain breaking effect on lipid peroxidation (LPO) and hence preventing the nitric oxide (NO) reservoir of ischemic tissue. Alfa-tocopherol may be a promising agent for the prevention of tissue injury caused by free oxygen radicals.
Biochem Mol Biol Int 1998 May
PMID:Effect of vitamin E on antioxidant enzymes and nitric oxide in ischemia-reperfused kidney injury. 962 81

Human amyotrophic lateral sclerosis (ALS), a typical motor neuron disease, is characterized pathologically by selective degenerative loss of motoneurons in the CNS. We have demonstrated significant reductions of neurotransmitter-related factors, such as acetylcholine-(ACh)-synthesizing enzyme activity and glutamate and aspartate contents in the ALS, compared to the non-ALS spinal cord obtained at autopsy. We have also shown considerable reductions in activities of cytochrome-c oxidase (CO), an enzyme contributing to aerobic energy production, and transglutaminase (TG), a Ca(2+)-dependent marker enzyme for tissue degeneration, in the ALS spinal cord. We found marked increases in fragmented glial fibrillary acidic protein (GFAP), a filamentous protein specifically associated with reactive astrocytes, in the ALS spinal cord relative to non-ALS tissue. These biochemical results corresponded well to pathomor-phological neuronal degenerative loss and reactive proliferation of astroglial components in the ALS spinal cord tissue. However, these results only indicate the final pathological and biochemical outcomes of ALS, and it is difficult to follow up cause and process in the ALS spinal cord during progression of the disease. Therefore, we used an animal model closely resembling human ALS, motor neuron degeneration (Mnd) mutant mice, a subline of C57BL/6 that shows late-onset progressive degeneration of lower motor neurons with paralytic gait beginning around 6.5 mo of age, to follow the biochemical and pathological alterations during postnatal development. We detected significant decreases in CO activity during early development and in activity of superoxide dismutase (SOD), an antioxidant enzyme, in later stages in Mnd mutant spinal cord tissue. TG activity in the Mnd spinal cord showed gradual increases during early development reaching a maximum at 5 mo, and then tending to decrease thereafter. Amounts of fragmented GFAPs increased continuously during postnatal development in Mnd spinal cord. These biochemical changes were observed prior to the appearance of clinical motor dysfunctions in the Mnd mutant mice. Such biochemical analyses using appropriate animal models will be useful for inferring the origin and progression of human ALS.
Mol Chem Neuropathol 1998 Apr
PMID:Neurochemical changes in the spinal cord in degenerative motor neuron diseases. 964 76

Nuclear factor-kappaB is a transcription factor that is activated in many different cell types by pathologic stimuli, such as reactive oxygen intermediates. One class of hepatocarcinogens, the peroxisome proliferators, may produce reactive oxygen intermediates, and one potent peroxisome proliferator, ciprofibrate, was recently reported to activate nuclear factor-kappaB. In this study, we investigated whether Dicamba, a broad leaf herbicide and peroxisome proliferator, could activate nuclear factor-KB in the livers of rats. Female and male Sprague Dawley rats (n = 4) were fed diets containing either 0, 1, or 3% Dicamba or 0.01% ciprofibrate for 7 days. As expected, the potent peroxisome proliferator, ciprofibrate, significantly increased fatty acyl CoA oxidase, peroxisomal beta-oxidation, and catalase activities in male rats and, except for catalase, also in female rats. Dicamba significantly increased peroxisomal fatty acyl CoA oxidase, peroxisomal beta-oxidation, and catalase activities, but decreased the activity of the cytosolic antioxidant enzyme, Se-dependent glutathione peroxidase, in both female and male rats. Dicamba increased nuclear factor-kappaB binding in the nuclear protein of livers from male rats fed both the 1 and 3% Dicamba diets. However, the highest binding was seen in nuclear protein from female rats fed 3% Dicamba. Both supershift and cold competition assays confirmed that this DNA binding activity was specific for nuclear factor-kappaB. Our results in this study suggest that the herbicide and peroxisome proliferator Dicamba has the ability to activate nuclear factor-kappaB.
J Biochem Mol Toxicol 1998
PMID:Activation of hepatic NF-kappaB by the herbicide Dicamba (2-methoxy-3,6-dichlorobenzoic acid) in female and male rats. 973 82

Mechanism of amyloid beta-peptide (A beta) toxicity in cultured neurons involves the development of oxidative stress in the affected cells. A significant increase in protein carbonyl formation was detected in cultured hippocampal neurons soon after the addition of preaggregated A beta(1-40), indicating oxidative damage of proteins. We report that neurons, subjected to A beta(1-40), respond to A beta oxidative impact by activation of antioxidant defense mechanisms and alternative ATP-regenerating pathway. The study demonstrates an increase of Mn SOD gene expression and the restoration of Cu, Zn SOD gene expression to a normal level after temporary suppression. Partial loss of creatine kinase (CK) BB activity, which is the key enzyme for functioning of the creatine/phosphocreatine shuttle, was compensated in neurons surviving the A beta oxidative attack by increased production of the enzyme. As soon as the oxidative attack triggered by the addition of preaggregated A beta (1-40) to rat hippocampal cell cultures has been extinguished, CK BB expression and SOD isoenzyme-specific mRNA levels in surviving neurons return to normal. We propose that the maintenance of a constant level of CK function by increased CK BB production together with the induction of antioxidant enzyme gene expression in A beta-treated hippocampal neurons accounts for at least part of their adaptation to A beta toxicity.
J Mol Neurosci 1998 Jun
PMID:Amyloid beta-peptide (1-40)-mediated oxidative stress in cultured hippocampal neurons. Protein carbonyl formation, CK BB expression, and the level of Cu, Zn, and Mn SOD mRNA. 977 Jun 41

The roles of enzymatic antioxidant defenses in the natural tolerance of environmental stresses that impose changes in oxygen availability and oxygen consumption on animals is discussed with a particular focus on the biochemistry of estivation and metabolic depression in pulmonate land snails. Despite reduced oxygen consumption and PO2 during estivation, which should also mean reduced production of oxyradicals, the activities of antioxidant enzymes, such as superoxide dismutase and catalase, increased in 30 day-estivating snails. This appears to be an adaptation that allows the snails to deal with oxidative stress that takes place during arousal when PO2 and oxygen consumption rise rapidly. Indeed, oxidative stress was indicated by increased levels of lipid peroxidation damage products accumulating in hepatopancreas within minutes after arousal was initiated. The various metabolic sites responsible for free radical generation during arousal are still unknown but it seems unlikely that the enzyme xanthine oxidase plays any substantial role in this despite being implicated in oxidative stress in mammalian models of ischemia/reperfusion. We propose that the activation of antioxidant defenses in the organs of Otala lactea during estivation is a preparative mechanism against oxidative stress during arousal. Increased activities of antioxidant enzymes have also observed under other stress situations in which the actual production of oxyradicals should decrease. For example, antioxidant defenses are enhanced during anoxia exposure in garter snakes Thamnophis sirtalis parietalis (10 h at 5 degrees C) and leopard frogs Rana pipiens (30 h at 5 degrees C) and during freezing exposure (an ischemic condition due to plasma freezing) in T. sirtalis parietalis and wood frogs Rana sylvatica. It seems that enhancement of antioxidant enzymes during either anoxia or freezing is used as a preparatory mechanism to deal with a physiological oxidative stress that occurs rapidly within the early minutes of recovery during reoxygenation or thawing. Thus, a wide range of stress tolerant animals display coordinated changes in antioxidant defenses that allow them to deal with oxidative stress that occurs as part of natural cycles of stress/recovery that alter oxygen levels in tissues. The molecular mechanisms that trigger and regulate changes in antioxidant enzyme activities in these species are still unknown but could prove to have key relevance for the development of new intervention strategies in the treatment of cardiovascular ischemia/reperfusion injuries in humans.
Comp Biochem Physiol B Biochem Mol Biol 1998 Jul
PMID:Antioxidant defenses and metabolic depression. The hypothesis of preparation for oxidative stress in land snails. 978 4

Effect of oral administration of aluminum sulphate (200 and 400 mg/kg body wt/day) without or with citric acid (62 mg/kg body wt/day) to day-old White Leghorn male chicks (n = 5 per group) for 30 days was studied on the activities of superoxide dismutase (SOD) and catalase, and level of lipid peroxidation in cerebral hemisphere and liver. A 400 mg dose of Al in the presence of citric acid inhibited cytosolic total and CN -sensitive superoxide dismutase activities of the cerebral hemisphere in 7- and 30-day treated chicks, whereas in 15-day treated chicks the enzyme activities were decreased in response to both doses in the presence of citric acid. In case of liver, activities of these enzymes significantly decreased after 7, 15 and 30 days of treatment with 200 and 400 mg Al together with citric acid, whereas 400 mg Al alone inhibited the enzyme activities after 15 and 30 days of treatment. Cerebral catalase activity decreased in response to 400 mg Al when the chicks were also fed with citric acid for 7 and 30 days, but in 15-day treated chicks the enzyme activity was depleted following treatment with 200 and 400 mg Al combined with citric acid. 400 mg Al treatment for 7 days in combination with citric acid inhibited hepatic catalase activity and extension of the treatment period to 15 and 30 days also produced reduction in its activity even in response to the lower Al dose mixed with citric acid. CN -insensitive SOD activity of cerebral hemisphere and liver was unaffected by Al. Al also failed to induce lipid peroxidation in both the tissues throughout the course of exposure. Activities of SOD and catalase of cerebral hemisphere and liver of 30-day old chicks were observed to be inhibited by in vitro incubation with different concentrations of Al. Our in vivo study demonstrates that only CN -sensitive SOD is susceptible to Al. Further, responses of SOD and catalase to Al is tissue specific. The observed inhibition of antioxidant enzyme activities by Al is suggestive of a prooxidant state. Induction of such an oxidative condition of the tissues may be attributed to a direct effect of the metal on enzyme molecules or in their synthesis.
Mol Cell Biochem 1998 Oct
PMID:Effects of aluminum sulphate and citric acid ingestion on lipid peroxidation and on activities of superoxide dismutase and catalase in cerebral hemisphere and liver of developing young chicks. 978 54

Thioredoxin reductase (TrxR) is one of a number of flavoproteins that catalyze the transfer of electrons between pyridine nucleotides and a specific disulfide-containing substrate. Thioredoxin reductase from Streptomyces aureofaciens 3239 has been purified to homogeneity by a two-step chromatographic procedure including anion-exchange chromatography and affinity chromatography on 2'5'-ADP-Sepharose 4B. Molar mass determined by chromatography on Superose 12 HR 10/30 and sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed 69 kDa for the native protein and 34.8 kDa for the enzyme subunit. The isoelectric point determined by isoelectric focusing gel electrophoresis was 4.3. TrxR effectively catalyzed the reduction of DTNB in the presence of S. aureofaciens thioredoxin-1. TrxR activity in the presence of S. aureofaciens thioredoxin-2 was only 1/4 of the activity with thioredoxin-1 (1). The activity of pure TrxR decreased drastically in the presence of NADPH, while NADP+ as well as Streptomyces aureofaciens thioredoxin-1 protected the enzyme from inactivation. These results indicate that thioredoxin reductase activity in bacteria could be modulated by the redox status of NADP+/NADPH and thioredoxin pools.
Biochem Mol Biol Int 1998 Nov
PMID:Purification and partial characterization of thioredoxin reductase from Streptomyces aureofaciens. 984 25

Our previous studies noted the oxidative stress of unilateral ureteral obstruction (UUO). Now, we seek to explore whether UUO affects the intrinsic cellular antioxidants and triggers heat shock protein (HSP-70) and whether these are still highly expressed after reversal of the UUO (R-UUO). In addition, we designed the experiment to determine whether this expression of HSP-70 is a localized or a generalized response. Male Sprague-Dawley rats (125-150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedures at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstructed) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was observed: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham in R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham values. It is possibly the result of a systemic effect from the free radicals produced by the oxidative stress of the UUO. The antioxidant enzyme, manganese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP-70 increased during UUO and was 3.7-fold that of sham (P < 0.05) but, during R-UUO, was not different from sham (P, ns). The contralateral (intact) right kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. We conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cellular antioxidant enzyme, manganese superoxide dismutase, showed a significant and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO or in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO.
Mol Genet Metab 1998 Dec
PMID:Increased heat shock protein-70 in unilateral ureteral obstruction in rats. 988 18

The transgenic mice overexpressing heat shock protein 72 (HSP72) or antioxidants have been reported to be more resistant to myocardial ischemia/reperfusion injury. However, it remains unknown whether whole body heat stress (HS) which may induce HSP72 or endogenous antioxidants affords similar protection in the mouse heart. Adult male mice were treated with either HS (42 degrees C for 15 min) or anesthesia only (SC) against a group of non-stressed controls (NC). At 6 or 24 h later, the hearts were excised and perfused at a constant pressure of 55 mmHg in Langendorff mode. Following 30 min equilibration, hearts were subjected to 20 min of global ischemia and 30 min reperfusion (37 degrees C). Ventricular force was measured by a force-displacement transducer attached to the apex. Leakage of intracellular enzymes (CK, LDH) was measured in coronary efflux. Infarct size was determined by tetrazolium staining. The results showed that no significant differences between HS, SC, and NC groups in ventricular contractile function, CK and LDH release, or infarct size were observed at either time window. HS enhanced the expression of HSP72 in mouse hearts by two- to three-fold, whereas antioxidant enzyme activities (catalase and MnSOD) did not change significantly. We conclude that HS does not precondition the isolated perfused mice hearts against ischemia/reperfusion injury, despite induction of HSP72.
J Mol Cell Cardiol 1998 Nov
PMID:Whole body heat shock fails to protect mouse heart against ischemia/reperfusion injury: role of 72 kDa heat shock protein and antioxidant enzymes. 992 59


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