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

Little is known about the antioxidant capacity and oxidant-generating potential of newborn muscle, or how these properties compare with the adult and relate to fatigue resistance. We determined the 1) antioxidant enzyme activities [superoxide dismutase (SOD), catalase, glutathione peroxidase], 2) glutathione content, 3) oxidative capacity [indexed by succinic dehydrogenase activity], 4) extracellular cytochrome c reduction, and 5) efficacy of exogenously administered SOD in ameliorating fatigue in vitro of newborn and adult diaphragm (DIA). Newborn and adult DIA SOD activities were not different, whereas newborn catalase activity was greater, and newborn glutathione peroxidase activity and glutathione content less than adult DIA. Succinic dehydrogenase activity was approximately 2-fold greater in the adult compared with the neonate. Repetitive contractions led to a significant decline in newborn and adult DIA force; this decline was greater in the adult (78 +/- 4% decrement in force at 2 min) compared with newborn DIA (28 +/- 8% decrement in force at 2 min). Extracellular cytochrome c reduction was greater in adult as compared with newborn DIA during fatiguing contractions. Exogenous SOD attenuated fatigue in the adult, but had no effect on newborn DIA. We conclude that the oxidative capacity of the adult DIA is greater than that of the newborn and not matched by a concomitant increase in SOD activity. Our data suggest that the increased oxidative capacity relative to SOD activity in adult DIA may lead to oxidative stress and an enhanced susceptibility to fatigue.
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PMID:Rat diaphragm oxidative capacity, antioxidant enzymes, and fatigue: newborn versus adult. 921 38

Cytochrome c peroxidase oxidises hydrogen peroxide using cytochrome c as the electron donor. This enzyme is found in yeast and bacteria and has been also described in the trematodes Fasciola hepatica and Schistosoma mansoni. Using partially purified cytochrome c peroxidase samples from Fasciola hepatica we evaluated its role as an antioxidant enzyme via the investigation of its ability to protect against oxidative damage to deoxyribose in vitro. A system containing FeIII-EDTA plus ascorbate was used to generate reactive oxygen species superoxide radical, H2O2 as well as the hydroxyl radical. Fasciola hepatica cytochrome c peroxidase effectively protected deoxyribose against oxidative damage in the presence of its substrate cytochrome c. This protection was proportional to the amount of enzyme added and occurred only in the presence of cytochrome c. Due to the low specific activity of the final partially purified sample the effects of ascorbate and calcium chloride on cytochrome c peroxidase were investigated. The activity of the partially purified enzyme was found to increase between 10 and 37% upon reduction with ascorbate. However, incubation of the partially purified enzyme with 1 mM calcium chloride did not have any effect on enzyme activity. Our results showed that Fasciola hepatica CcP can protect deoxyribose from oxidative damage in vitro by blocking the formation of the highly toxic hydroxyl radical (.OH). We suggest that the capacity of CcP to inhibit .OH-formation, by efficiently removing H2O2 from the in vitro oxidative system, may extend the biological role of CcP in response to oxidative stress in Fasciola hepatica.
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PMID:Characterisation of Fasciola hepatica cytochrome c peroxidase as an enzyme with potential antioxidant activity in vitro. 1040 59

Treatment of WEHI7.2 cells, a mouse thymoma-derived cell line, with dexamethasone, a synthetic glucocorticoid, causes the cells to undergo apoptosis. Previous work has shown that treatment of WEHI7.2 cells with dexamethasone results in a downregulation of antioxidant defense enzymes, suggesting that increased oxidative stress may play a role in glucocorticoid-induced apoptosis. To test whether resistance to oxidative stress causes resistance to dexamethasone-induced apoptosis, WEHI7.2 cell variants selected for resistance to 50, 100 and 200 microM H(2)O(2) were developed. Resistance to H(2)O(2) is accompanied by increased antioxidant enzyme activity, resistance to other oxidants and a delayed loss of viable cells after dexamethasone treatment. In the 200 microM H(2)O(2)-resistant cell variant the delay in cell loss is correlated with delayed release of cytochrome c from the mitochondria into the cytosol. This suggests that reactive oxygen species play a role in a signaling event during steroid-mediated apoptosis in lymphocytes.
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PMID:Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis. 1152 50

We investigate the death route induced by potassium depletion in cerebellar granule cells in 0-15 h time range and study whether and how mutual relationship occurs between the cell antioxidant and proteolytic system. To achieve this, we incubated cells in the absence or presence of inhibitors of the antioxidant system, including superoxide dismutase and catalase, and of the proteolytic system, consisting of proteasomes and caspases, and investigated whether and how (i) cell survival, (ii) reactive oxygen species (ROS) production and (iii) antioxidant enzyme and caspase-3 activity change as a function of time after the apoptotic stimulus. The involvement of both antioxidant and proteolytic system on cytochrome c release was also investigated. Cell survival was found to increase in the presence of either proteasome or caspase inhibitors. On the contrary, as a result of the antioxidant system impairment, shift from apoptosis to necrosis occurs. We show that the antioxidant system, which exhibits a huge activity increase up to 3 h after apoptosis induction, is subjected to the proteasome-dependent proteolysis and that the increase in the antioxidant system found in the absence of proteasome activity is accompanied by ROS production decrease. Consistently, the early ROS-dependent release of cytochrome c was found to be prevented when the activity of the antioxidant system increased. Finally, caspase-3 activation was prevented by the inhibitors of both antioxidant system and proteasome.
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PMID:The apoptosis/necrosis transition in cerebellar granule cells depends on the mutual relationship of the antioxidant and the proteolytic systems which regulate ROS production and cytochrome c release en route to death. 1260 21

The pharmacological properties of garlic and its derivatives are long known, and their underling mechanisms are being extensively investigated. In this study we have addressed the effects of diallyl disulfide (DADS), an oil-soluble garlic molecule, on cell growth of neuroblastoma cell SH-SY5Y, focusing on the redox events associated with this compound. Treatment of SH-SY5Y cells with DADS resulted in arrest of cell cycle in G(2)/M phase and commitment to apoptosis through the activation of the mitochondrial pathway (Bcl-2 down-regulation, cytochrome c release into the cytosol, and activation of caspase-9 and caspase-3). The earliest oxidative event observed after DADS treatment was the increase of production of reactive oxygen species, which reached the maximum yield on 30 min of DADS treatment. The oxidative burst resulted in protein and lipid damage as demonstrated by protein carbonyl accumulation and lipid peroxidation. We demonstrated that apoptosis induction was highly dependent on the activation of the redox-sensitive c-Jun NH(2)-terminal kinase (JNK)/c-Jun pathway. In particular, we established that DADS treatment induces JNK dissociation from glutathione S-transferase and its activation by phosphorylation. Moreover, treatment with JNK inhibitor I significantly reduced DADS-induced apoptosis and treatment with the spin trap 5,5'-dimethyl-1-pyrroline N-oxide or overexpression of the antioxidant enzyme copper, zinc superoxide dismutase, resulted in the inhibition of DADS-mediated toxicity through attenuation of JNK/c-Jun pathway activation. Overall, the results suggest a pivotal role for oxidative stress in DADS-induced apoptosis and, taking into account that tumor cells are deficient in antioxidants, suggest a plausible utilization of this compound as an antiproliferative agent in cancer therapy.
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PMID:Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide. 1452 20

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a unique antioxidant enzyme that markedly reduces lipid hydroperoxide generated in biomembranes. Overexpression of mitochondrial PHGPx potentially suppresses the release of cytochrome c (cyt. c) from mitochondria and apoptosis. The hydroperoxide level in mitochondria was elevated in 2-deoxyglucose (2DG)-induced apoptosis, but not in apoptosis-resistant cells in which mitochondrial PHGPx was overexpressed. From studies of the overexpression of PHGPx, the generation of hydrogen peroxide and lipid hydroperoxide in mitochondria might be important triggers of apoptosis. In particular lipid hydroperoxide could be involved in the initiation of cyt. c liberation from mitochondria in 2DG-induced apoptosis since lipid hydroperoxide is a primary substrate for PHGPx. The release of cyt. c from mitochondria is an important proapoptotic signal in the mitochondrial death pathway. Several reports demonstrated the reactive oxgen species could be involved in cyt. c liberation, although its mechanism is still unknown. Cardiolipin (CL), which exclusively locates in the innermembrane of mitochondria, shows strong affinity for cyt. c is required for the adenine nucleotide translocator (ANT) that controls the opening and closing of the permeability transition pore. Association of cyt. c with CL is lost upon peroxidation. CL hydroperoxide (CLOOH), in contrast to CL, does not bind to cyt. c. Furthermore, CLOOH can open the permeability transion pore by the inactivation of ANT. These previous results suggest that mitochondrial PHGPx inhibits the release of cyt. c from mitochondria by the scavenging CLOOH and could prevent apoptosis.
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PMID:Role of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx) as an antiapoptotic factor. 1525 21

Excessive production of reactive oxygen species (ROS) may lead to oxidative stress, loss of cell function, and cell death by apoptosis or necrosis. Recently, ROS have gained attention as important second messengers. ROS lifetimes can be very short, and many types of ROS cannot penetrate organelle membranes. It is therefore thought that only ROS signal molecules that are generated locally in an organelle are transduced when cells are stimulated. Lipid hydroperoxides are one type of ROS of which the biological function has not yet been clarified. The phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) is a unique antioxidant enzyme and separately distributed to the mitochondria, nucleus, nucleoli, and cytosol, where it regulates phospholipid hydroperoxide and fatty acid hydroperoxide as signal molecules. This review focuses on the structure and biological functions of PHGPx in mammalian cells. Overexpression of different types of PHGPx in the RBL2H3 cell line provides a useful model system with which to clarify the ability of different types of PHGPx to modulate cellular function and the importance of lipid hydroperoxides as signal molecules. Transformant studies show that lipid hydroperoxide is an activator of lipoxygenase and cyclooxygenase and participates in inflammation, cardiolipin hydroperoxide is the signal molecule for the release of cytochrome c during apoptotic cell death, and PHGPx is a signal regulator in the IgE receptor-mediated signaling pathway. It is becoming clear that PHGPx has an important role in spermatogenesis, sperm function, and embryonic development, and its deficiency is implicated in human infertility and in embryonic lethality of PHGPx knockout mice.
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PMID:[Biological significance of lipid hydroperoxide and its reducing enzyme, phospholipid hydroperoxide glutathione peroxidase, in mammalian cells]. 1557 64

Apoptosis can be evoked by reactive oxygen species (ROS)-induced mitochondrial release of the proapoptotic factors cytochrome c and apoptosis-inducing factor (AIF). Because skeletal muscle is composed of two mitochondrial subfractions that reside in distinct subcellular regions, we investigated the apoptotic susceptibility of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS and IMF mitochondria exhibited a dose-dependent release of protein in response to H2O2 (0, 25, 50, and 100 microM). However, IMF mitochondria were more sensitive to H2O2 and released a 2.5-fold and 10-fold greater amount of cytochrome c and AIF, respectively, compared with SS mitochondria. This finding coincided with a 44% (P < 0.05) greater rate of opening (maximum rate of absorbance decrease, V(max)) of the protein release channel, the mitochondrial permeability transition pore (mtPTP), in IMF mitochondria. IMF mitochondria also exhibited a 47% (P < 0.05) and 60% (0.05 < P < 0.1) greater expression of the key mtPTP component voltage-dependent anion channel and cyclophilin D, respectively, along with a threefold greater cytochrome c content, but similar levels of AIF compared with SS mitochondria. Despite a lower susceptibility to H2O2-induced release, SS mitochondria possessed a 10-fold greater Bax-to-Bcl-2 ratio (P < 0.05), a 2.7-fold greater rate of ROS production, and an approximately twofold greater membrane potential compared with IMF mitochondria. The expression of the antioxidant enzyme Mn2+-superoxide dismutase was similar between subfractions. Thus the divergent protein composition and function of the mtPTP between SS and IMF mitochondria contributes to a differential release of cytochrome c and AIF in response to ROS. Given the relatively high proportion of IMF mitochondria within a muscle fiber, this subfraction is likely most important in inducing apoptosis when presented with apoptotic stimuli, ultimately leading to myonuclear decay and muscle fiber atrophy.
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PMID:Differential susceptibility of subsarcolemmal and intermyofibrillar mitochondria to apoptotic stimuli. 1590 2

This study was carried out to evaluate the hepatoprotective activity of glycoprotein isolated from the stems of Ulmus davidiana Nakai (UDN), which has been used as an anti-inflammatory agent in folk medicine. We evaluated lipid peroxidation in glucose/glucose oxidase (G/GO)-induced BNL CL.2 cells and measured thiobarbituric acid reactive substances (TBARS), lactate dehydrogenase (LDH), nitric oxide (NO), antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), activity of cytotoxic-related signals (hepatic cytochrome c, nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1)) and levels of plasma lipids (triglyceride (TG) and total cholesterol (TC)) in carbon tetrachloride (CCl(4,) 1.0 mL kg(-1))-induced A/J mouse. The results in G/GO-induced BNL CL.2 cells showed that UDN glycoprotein had a dose-dependent inhibitory effect on lipid peroxidation. The results in carbon tetrachloride (CCl(4,) 1.0 mL kg(-1))-induced A/J mouse indicated that treatment with UDN glycoprotein (40 mg kg -1) lowered LDH activity and TBARS formation, and increased NO production and antioxidant enzymes activity, compared with control. Also, our finding from CCl(4)-treated mice after pretreatment with UDN glycoprotein demonstrated that the activity of cytotoxic-related signals decreased but the levels of plasma lipids increased, compared with CCl(4) treatment alone. Here, we speculate that UDN glycoprotein has a protective character to CCl(4)-induced mouse liver injury.
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PMID:Protective effect of glycoprotein isolated from Ulmus davidiana Nakai on carbon tetrachloride-induced mouse liver injury. 1639 75

In addition to playing a fundamental role in diverse processes, such as vision, growth and differentiation, vitamin A and its main biologically active derivative, retinoic acid (RA), are clearly involved in the regulation of testicular functions. The present study was undertaken to examine the direct effect of RA treatment on Leydig (TM-3) cells. TM-3 cells were cultured and treated with varying concentrations of RA for 24h. High doses of RA (1-20microM) induced a decrease in cell vitality and an increase in lipid peroxidation. RA treatment also induced a corresponding increase in apoptosis in the same cells in a dose-dependent manner. Apoptosis proceeded via the mitochondrial dependent pathway, as demonstrated by the release of cytochrome c, caspase-3 enzymatic activation and DNA fragmentation. Conversely, at physiological doses (0.1-500nM) RA did not increase lipid peroxidation or cell death and resulted in an increase of antioxidant enzyme activity.
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PMID:All-trans-retinoic acid induces apoptosis in Leydig cells via activation of the mitochondrial death pathway and antioxidant enzyme regulation. 1866 54


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