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)

Huntington's disease (HD) is a neurodegenerative disorder that results from the destruction of neurons in the basal ganglia, and oxidative stress has been implicated in its pathogenesis. 3-Nitropropionic acid (3-NP), a potent neurotoxin, has been reported to induce oxidative/nitrosative stress and causes neurobehavioral and biochemical changes that mimic HD in humans. It also inhibits complex II of the mitochondrial electron transport chain, thereby causing cellular energy deficit. In the present work, we evaluated the effects of a well-known antioxidant on behavioral, biochemical, and mitochondrial dysfunction induced by 3-NP. The study was designed to investigate the effects of Withania somnifera root extract against 3-NP-induced gait abnormalities, oxidative stress, and mitochondrial dysfunction in striatum and cortex of rat brain. Intraperitoneal administration of 3-NP (10 mg/kg for 14 days) caused a loss in body weight and a decline in motor function (locomotor activity and impaired rotarod activity). Chronic treatment with W. somnifera root extracts (100 and 200 mg/kg) for a period of 2 weeks dose-dependently improved 3-NP-induced behavioral, biochemical, and enzymatic changes (P < .05). Biochemical analysis revealed that systemic 3-NP administration significantly increased lipid peroxidation and nitrite and lactate dehydrogenase enzyme levels, depleted antioxidant enzyme (superoxide dismutase and catalase) levels, and blocked ATP synthesis by inhibiting the mitochondrial complex activity in the different regions (striatum and cortex) of the brain. Chronic administration of W. somnifera root extract (100 and 200 mg/kg) dose-dependently restored biochemical alterations induced by chronic 3-NP treatment (P < .05). These findings suggest that neuroprotective actions of W. somnifera are mediated via its antioxidant activity. However, further studies are required to elucidate the molecular mechanisms involved in order to support the clinical use of the plant extract as a therapeutic agent for the treatment of HD.
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PMID:Possible neuroprotective effect of Withania somnifera root extract against 3-nitropropionic acid-induced behavioral, biochemical, and mitochondrial dysfunction in an animal model of Huntington's disease. 1962 8

Cornuside, a secoiridoid glucoside compound, was isolated from the fruit of Cornus officinalis Sieb. et Zucc. The present study elucidates the effects of cornuside on cultured rat cortical neuron damage induced by oxygen-glucose deprivation. The results show that cornuside treatment obviously attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons by increasing the cell survival rate, mitochondrial antioxidant enzyme activities, mitochondrial respiratory enzyme activity, mitochondrial respiratory control ratio and the ATP content, and by decreasing the mitochondrial malondialdehyde content, lactate dehydrogenase leakage rate, intracellular Ca(2+) level and caspase-3 activity in a concentration-dependent manner. These findings indicate that cornuside has protective potential against cerebral ischemic injury, and its protective effects may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.
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PMID:Cornuside attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons. 1969 22

In fast- and slow-twitch limb and heart muscles of cachectic rats, redox balance and muscle structure were explored. The nature of the oxidatively modified proteins also was identified in these muscles. Reactive carbonyls, hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and antioxidant enzyme levels were determined in limb and heart muscles of cachectic (7 days after inoculation of Yoshida AH-130 ascites hepatoma) and control rats. Moreover, carbonylated proteins were identified (proteomics), and fiber-type composition evaluated (morphometry) in these muscles. In cachectic rats, compared with the controls: (a) HNE- and MDA-protein adducts levels were greater in gastrocnemius, tibialis anterior, soleus, and heart; (b) in the gastrocnemius, type II fiber size was reduced, and the intensity of carbonylated protein immunostaining was significantly greater in these fibers; and (c) proteins involved in glycolysis, ATP production and distribution, carbon dioxide hydration, muscle contraction, and mitochondrial metabolism were significantly more carbonylated in limb and heart muscles. Cancer cachexia alters redox balance in fast- and slow-twitch limb and heart muscles of rats, inducing increased oxidative modifications of key proteins involved in muscle structure and function. Additionally, it induces a reduction in type II fiber size in the gastrocnemius, which is associated with increased protein oxidation.
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PMID:Redox balance and carbonylated proteins in limb and heart muscles of cachectic rats. 1973 87

Oxidative stress can damage the active site cysteine of the antioxidant enzyme peroxiredoxin (Prx) to the sulfinic acid form, Prx-SO(2)(-). This modification leads to inactivation. Sulfiredoxin (Srx) utilizes a unique ATP-Mg(2+)-dependent mechanism to repair the Prx molecule. Using selective protein engineering that involves disulfide bond formation and site-directed mutagenesis, a mimic of the enzyme.substrate complex has been trapped. Here, we present the 2.1 A crystal structure of human Srx in complex with PrxI, ATP, and Mg(2+). The Cys(52) sulfinic acid moiety was substituted by mutating this residue to Asp, leading to a replacement of the sulfur atom with a carbon atom. Because the Srx reaction cannot occur, the structural changes in the Prx active site that lead to the attack on ATP may be visualized. The local unfolding of the helix containing C52D resulted in the packing of Phe(50) in PrxI within a hydrophobic pocket of Srx. Importantly, this structural rearrangement positioned one of the oxygen atoms of Asp(52) within 4.3 A of the gamma-phosphate of ATP bound to Srx. These observations support a mechanism where phosphorylation of Prx-SO(2)(-) is the first chemical step.
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PMID:Protein engineering of the quaternary sulfiredoxin.peroxiredoxin enzyme.substrate complex reveals the molecular basis for cysteine sulfinic acid phosphorylation. 1981 42

ABSTRACT The findings in this study were that the exposure of FG cells to nonylphenol (NP) caused decreases in the cell growth rate, antioxidant enzyme activities, and ATP content; an increase in intracellular O(2)(-) content; and alteration of the organelles such as mitochondria and the RER. It is proposed that the reduction in antioxidant enzyme activities leads to accumulation of O(2)(-) content, which in turn results in the damage of mitochondrial infrastructures and a decline in energy production, which then causes the ultrastructural alterations in the cells. In addition, we show that FG cells are a good candidate system for evaluation of NP acute toxicities.
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PMID:Nonylphenol Causes Decrease in Antioxidant Enzyme Activities, Increase in O(2)(-) Content, and Alteration in Ultrastructures of FG Cells, a Flounder (Paralichthys olivaceus) Gill Cell Line. 2002 Sep 61

Atrazine (ATZ) is the most common pesticide of freshwater ecosystems in the world. The effects of ATZ exposure on the induction of oxidative stress and the alteration of gene expression were studied in liver and ovary samples from female zebrafish (Danio rerio). Antioxidant enzyme activities (SOD and CAT), in addition to the GSH and MDA content, in the liver altered significantly; the mRNA levels for the genes encoding these antioxidant proteins, such as Cu/Zn-Sod, Mn-Sod, Cat, and Gpx, were up-regulated significantly in the liver when zebrafish were exposed to various concentrations of ATZ for 14d. However, the mRNA induction patterns were not in accordance with those of antioxidant enzyme changes in the liver and ovary. Moreover, the transcriptional expression of mitochondrial inner membrane genes related to ROS production, such as Ucp-2 and Bcl-2, were altered significantly in high ATZ treatment groups. However, the ATZ treatment did not induce any apparent changes in the transcriptional expression of CoxI, Ndi, or ATPo6, which are related to the mitochondrial respiratory chain and ATP synthesis. To our knowledge, this is the first report to study the transcriptional effects of ATZ stress on zebrafish. The information presented in this study will be helpful in fully understanding the mechanism of oxidative stress induced by ATZ in fish.
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PMID:Oxidative stress response and gene expression with atrazine exposure in adult female zebrafish (Danio rerio). 2003 12

Reversible uncoupling of the mitochondrial electron-transport chain may be one strategy to prevent intracellular oxidative stress during liver cold preservation/warm reperfusion (CP/WR) injury. 2,4-Dinitrophenol (DNP) is a potent water-soluble uncoupling agent for supplementation of the hepatic CP solution. The aim of this work was to investigate the possible influence of DNP in the CP solution on the isolated rat liver state during CP/WR. Livers were subjected to CP at 4 degrees C in sucrose-phosphate based solution (SPS) for 18 h, followed by WR for 60 min in vitro. The final concentration of DNP was 100 microM. DNP presence during the CP stage led to partial ATP level decrease accompanied by a significant diminution in liver TBARS and a prevention of antioxidant enzyme activity decrease (catalase, GSH-PO, GSH-Red) when compared with livers stored without DNP. After DNP wash-out during WR, an improvement in the mitochondrial functional state (higher respiratory control indices and ATP levels, and a decrease in V(4) respiration rates) were observed. This was concurrent with lower TBARS levels, higher antioxidant enzyme activities and significant increase of bile production. The results suggest that reversible uncoupling may be one way to influence oxidative stress associated with hepatic cold preservation.
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PMID:Reversible mitochondrial uncoupling in the cold phase during liver preservation/reperfusion reduces oxidative injury in the rat model. 2015 23

The mechanisms responsible for anti-arrhythmic protection during ischemia-reperfusion (IR) in exercised hearts are not fully understood. The purpose of this investigation was to examine whether the ATP-sensitive potassium channels in the mitochondria (mito K(ATP)) and sarcolemma (sarc K(ATP)) provide anti-arrhythmic protection in exercised hearts during IR. Male Sprague-Dawley rats were randomly assigned to cardioprotective treadmill exercise or sedentary conditions before IR (I = 20 min, R = 30 min) in vivo. Subsets of exercised animals received pharmacological inhibitors for mito K(ATP) (5-hydroxydecanoate) or sarc K(ATP) (HMR1098) before IR. Blinded analysis of digital ECG tracings revealed that mito K(ATP) inhibition blunted the anti-arrhythmic effects of exercise, while sarc K(ATP) inhibition did not. Endogenous antioxidant enzyme activities for total, CuZn, and Mn superoxide dismutase, catalase, and glutathione peroxidase from ischemic and perfused ventricular tissue were not mitigated by IR, although oxidative stress was elevated in sedentary and mito K(ATP)-inhibited hearts from exercised animals. These findings suggest that the mito K(ATP) channel provides anti-arrhythmic protection as part of exercise-mediated cardioprotection against IR. Furthermore, these data suggest that the observed anti-arrhythmic protection may be associated with preservation of redox balance in exercised hearts.
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PMID:Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts. 2043 52

The quote "what does not kill you makes you stronger" perfectly describes the preconditioning phenomenon - a paradigm that affords robust brain tolerance in the face of neurodegenerative insults. Over the last few decades, many attempts have been made to identify the molecular mechanisms involved in preconditioning-induced protective responses, and recent data suggests that many of these mechanisms converge on the mitochondria, positing mitochondria as master regulators of preconditioning-triggered endogenous neuroprotection. In this review, we critically discuss evidence for the involvement of mitochondria within the preconditioning paradigm. We will highlight the crucial targets and mediators by which mitochondria are integrated into neuroprotective signaling pathways that underlie preconditioning, putting focus on mitochondrial respiratory chain and mitochondrial reactive oxygen species, mitochondrial ATP-sensitive potassium channels, mitochondrial permeability transition pore, uncoupling proteins, and mitochondrial antioxidant enzyme manganese superoxide dismutase. We also discuss the role of mitochondria in the induction of hypoxia-inducible factor-1, a transcription factor engaged in preconditioning-mediated neuroprotective effects. The identification of intrinsic mitochondrial mechanisms involved in preconditioning will provide new insights which can be translated into potential pharmacological interventions aimed at counteracting neurodegeneration.
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PMID:Mitochondria: the missing link between preconditioning and neuroprotection. 2046 94

The aim of this study was to investigate whether Rhodiola crenulata extract and tyrosol, a major bioactive phenolic compound present in Rhodiola, change the activities of endogenous antioxidant enzyme response (AER) and energy pathways linked to proline-mediated pentose phosphate pathway (PPP) during adipogenesis. Treatment with Rhodiola extracts inhibited the activities of proline dehydrogenase (PDH) and glucose-6-phosphate dehydrogenase (G6PDH) as well as lipid accumulation and reactive oxygen species (ROS) production. The inhibition of PDH and G6PDH activities by Rhodiola likely prevented proline oxidation required for critical ATP generation that is coupled to AER via the PPP, leading to inhibition of adipogenesis. Rhodiola extracts dose-dependently increased superoxide dismutase (SOD) activity, resulting in a reduced ROS level during adipogenesis. Moreover, the effects of tyrosol, a major bioactive compound in Rhodiola species, were directly correlated with all observed effects by Rhodiola extracts. These results indicate that the antiadipogenic effects of Rhodiola extracts can be attributed to a phenolic tyrosol that may potentially disrupt proline-mediated energy generation and AER via PPP, resulting in the suppression of adipogenesis and lipid accumulation. This further provides a biochemical rationale to identify the roles of phenolics that modulate the cellular redox environment and therefore have relevance for obesity management.
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PMID:Rhodiola-induced inhibition of adipogenesis involves antioxidant enzyme response associated with pentose phosphate pathway. 2062 18


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