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)

Steroid hormones have been reported to activate various signal transducers that trigger a variety of cellular responses. Among these hormones, testosterone has been identified as an antioxidant that protects against cellular damage. Therefore, using mouse embryonic stem (ES) cells as a model system, this study evaluated the effects of dihydrotestosterone (DHT), a biologically active testosterone metabolite, on H2O2-induced apoptosis. H2O2 increased the release of lactate dehydrogenase (LDH) and DNA fragmentation but reduced the cell viability in a time-dependent manner (> or =8 h). Moreover, H2O2 decreased the level of DNA synthesis and the levels of the cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H2O2 were inhibited by a pretreatment with DHT. However, a treatment with flutamide (androgen receptor inhibitor, 10(-3) M) abolished the protective effects of DHT. This result was supported by the presence of the androgen receptor in mouse ES cells. The activity of the antioxidant enzyme, catalase, was increased by the DHT treatment but not by a co-treatment with DHT and flutamide. Using CM-H(2)DCFDA (DCF-DA) for the detection of intracellular H2O2, DHT decreased the intracellular H2O2 levels but flutamide blocked this effect. H2O2 also increased the level of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation, which were inhibited by the DHT pretreatment. Catalase inhibited the effect of H2O2 on MAPKs and NF-kappaB. However, the flutamide treatment abolished the inhibitory effects of DHT on the H2O2-induced increase in the levels of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation. DHT inhibited the H2O2-induced increase in caspase-3 expression and decreased the level of Bcl-2 and the cellular inhibitor of apoptosis protein (cIAP)-2. These effects were abolished by the flutamide treatment. In conclusion, DHT prevents the H2O2-induced apoptotic cell death of mouse ES cells through the activation of catalase and the downregulation of p38 MAPK, JNK/SAPK, and NF-kappaB via the androgen receptor.
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PMID:Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. 1833 Aug 93

Diallyl sulfide, a sulfur-containing volatile compound present in garlic (Allium sativum), exerts anticarcinogenic activity in various rodent tumor models. In the present study, apoptosis-inhibiting effects of diallyl sulfide against a carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethyl benz(a)anthracene (DMBA), in Swiss albino mice were observed. The animals were given either 250 microg/mouse or 500 mug/mouse of diallyl sulfide for 1 week after a single intragastric dose of 7,12-dimethyl benz(a)anthracene (50 mg/kg body weight). Results showed that diallyl sulfide supplementation effectively protects against 7,12-dimethyl benz(a)anthracene-induced oxidative stress, characterized by restored antioxidant enzyme levels (up to 64%) and lipid peroxidation (up to 25%). Flow cytometric analysis showed a reduction in apoptotic cell population in hypodiploid region in diallyl sulfide-supplemented animals. Inhibition of apoptosis was preceded by decrease in reactive oxygen species levels and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In 7,12-dimethyl benz(a)anthracene-exposed animals, downregulation approximately 30%) of antiapoptotic Bcl-2 and upregulation (approximately 60%) of pro-apoptotic Bax proteins were observed. These alterations were restored significantly by diallyl sulfide supplementation, indicating inhibition of apoptosis. Thus, these results show that diallyl sulfide provides protection against oxidative damage induced by 7,12-dimethyl benz(a)anthracene in mouse liver and may be an effective chemopreventive and therapeutic agent by modulating expression of cell-growth regulatory proteins.
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PMID:Regulation of oxidative stress-mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice. 1848 Jan 50

In this study, we investigated the protective effects of rosmarinic acid (RA) on H(2)O(2)-induced neurotoxicity in human dopaminergic cell line, SH-SY5Y. Results showed that RA significantly attenuated H(2)O(2)-induced reactive oxygen species (ROS) generation and apoptotic cell death. Rosmarinic acid effectively suppressed the up-regulation of Bax and down-regulation of Bcl-2. Furthermore, RA stimulated the antioxidant enzyme heme oxygenase-1 (HO-1). We also demonstrated that the HO-1 induction by RA was associated with the protein kinase A (PKA) and phosphatidylinositiol-3-kinase (PI3K) signaling pathways. These results suggest that RA can protect SH-SY5Y cells under oxidative stress conditions by regulating apoptotic process. Thus, RA should be clinically evaluated for the prevention of neurodegenerative diseases.
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PMID:Rosmarinic acid protects human dopaminergic neuronal cells against hydrogen peroxide-induced apoptosis. 1864 21

Thioredoxin reductase (TrxR) is a key selenoprotein antioxidant enzyme and a potential target for anti-cancer drugs. One potent inhibitor of TrxR is the gold (I) compound auranofin, which can trigger mitochondrial-dependent apoptosis pathways. The exact mechanism of apoptosis induction by auranofin is not yet clear, but there are indications that mitochondrial oxidative stress is a central event. We assessed the redox state of the peroxiredoxins (Prxs) in Jurkat T-lymphoma cells treated with auranofin, and found that mitochondrial Prx3 was considerably more sensitive to oxidation than the cytosolic Prx1 and 2, indicating selective mitochondrial stress. Prx3 oxidation was detected at apoptotic doses of auranofin in several cell types, and occurred before other mitochondrial events including cytochrome c release and mitochondrial depolarisation. Auranofin was also able to sensitise U937 cells to TNF-alpha-mediated apoptosis. Auranofin-induced apoptosis was effectively blocked by the overexpression of Bcl-2, and Bax/Bak deficient mouse embryonic fibroblasts were also resistant to apoptosis, indicating a central role for the pro-apoptotic proteins of this family in auranofin-triggered apoptosis. Auranofin exposure inhibited the proliferation of apoptosis-resistant cells, and at higher doses of auranofin could cause cell death through necrosis. We conclude that auranofin induces apoptosis in cells through a Bax/Bak-dependent mechanism associated with selective disruption of mitochondrial redox homeostasis in conjunction with oxidation of Prx3.
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PMID:The thioredoxin reductase inhibitor auranofin triggers apoptosis through a Bax/Bak-dependent process that involves peroxiredoxin 3 oxidation. 1878 12

Peroxiredoxin II, a cytosolic isoform of the antioxidant enzyme family, has been implicated in cancer-associated cell death and apoptosis, but its functional role in the heart remains to be elucidated. Interestingly, the expression levels of peroxiredoxin II were decreased in mouse hearts upon ischemia-reperfusion, while they were elevated in two genetically modified hyperdynamic hearts with phospholamban ablation or protein phosphatase 1 inhibitor 1 overexpression. To delineate the functional significance of altered peroxiredoxin II expression, adenoviruses encoding sense or antisense peroxiredoxin II were generated; cardiomyocytes were infected, and then subjected to H(2)O(2) treatment to mimic oxidative stress-induced cell death and apoptosis. H(2)O(2) stimulation resulted in a significant decrease of endogenous peroxiredoxin II expression, along with reduced cell viability in control cells. However, overexpression of peroxiredoxin II significantly protected from H(2)O(2)-induced apoptosis and necrosis, while downregulation of this enzyme promoted the detrimental effects of oxidative stress in cardiomyocytes. The beneficial effects of peroxiredoxin II were associated with increased Bcl-2 expression, decreased expression of Bax and attenuated activity of caspases 3, 9 and 12. Furthermore, there were no significant alterations in the expression levels of the other five isoforms of peroxiredoxin, as well as active catalase or glutathione peroxidase-1 after ischemia-reperfusion or H(2)O(2) treatment. These findings suggest that peroxiredoxin II may be a unique antioxidant in the cardiac system and may represent a potential target for cardiac protection from oxidative stress-induced injury.
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PMID:Protection of peroxiredoxin II on oxidative stress-induced cardiomyocyte death and apoptosis. 1903 Sep 11

The aims of this study were to assess the effects of a swimming session on the peripheral blood neutrophil and lymphocyte pro- and antioxidant system, identify any differences between the sexes and the regulatory mechanisms that might induce the immune cell adaptive response to exercise. Twenty-four swimmers (15 males, 9 females) participated in a one-hour swimming session at 75-80% of their maximal capacity. The session induced neutrophilia and decreased antioxidant enzyme activities and ascorbate levels in neutrophils. Malondialdehyde rose in neutrophils in males and females, whereas the carbonyl index only increased in males. Lymphocyte glutathione peroxidase activity was higher in males at baseline and rose as a consequence of exercise. The exercise decreased uncoupling protein-3 and Bcl-2 gene expression. The expression of PPARgamma coactivator-1 alpha (PGC-1alpha) correlated positively with that of sirtuin 3 (SIRT3) and catalase. In summary, a swimming session of one hour at 75-80% of maximal capacity produced oxidative damage in neutrophils and induced the antioxidant defences in lymphocytes. PGC-1alpha and SIRT3 appear to be key effectors of this adaptive response in lymphocytes. Both the neutrophil and lymphocyte response to exercise were slightly weaker in females than males.
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PMID:Antioxidant regulatory mechanisms in neutrophils and lymphocytes after intense exercise. 1903 35

Atherosclerosis is a chronic inflammatory process with increased oxidative stress in vascular endothelium. Ginkgo biloba extract (GbE), extracted from Ginkgo biloba leaves, has commonly been used as a therapeutic agent for cardiovascular and neurological disorders. The aim of this study was to investigate how GbE protects vascular endothelial cells against the proatherosclerotic stressor oxidized low-density lipoprotein (oxLDL) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5-100 microg/ml) for 2 h and then incubated with oxLDL (150 microg/ml) for an additional 24 h. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability, and several apoptotic indexes were assessed. Our data show that ROS generation is an upstream signal in oxLDL-treated HUVECs. Cu,Zn-SOD, but not Mn-SOD, was inactivated by oxLDL. In addition, oxLDL diminished expression of endothelial NO synthase and enhanced expression of adhesion molecules (ICAM, VCAM, and E-selectin) and the adherence of monocytic THP-1 cells to HUVECs. Furthermore, oxLDL increased intracellular calcium, disturbed the balance of Bcl-2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by GbE (P < 0.05). Results from this study may provide insight into a possible molecular mechanism underlying GbE suppression of the oxLDL-mediated vascular endothelial dysfunction.
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PMID:Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells. 1922 86

The polysaccharides from Ganoderma lucidum (GLP) were prepared using boiling water extraction methods. High performance liquid chromatography (HPLC) showed that GLP was composed of five monosaccharides and disaccharides, including xylose, fructose, glucose, sucrose and maltose, were identified for polysaccharides from Ganoderma lucidum. The relative molar percentages of xylose, fructose, glucose, sucrose and maltose in polysaccharides from Ganoderma lucidum were 0.4%, 14.4%, 12.8%, 0.7% and 50.9%, respectively. GLP (100, 200, 300mg/kg) was administered to diabetic rats. Effect of extract on antioxidant enzymes activities and lipid peroxidation levels of pancreas was studied in diabetic rats. The mechanism of anti-apoptosis of GLP in STZ-induced diabetic rats was further investigated using Bax/Bcl-2 ratio and protein. Result showed that GLP extracts effectively reduced oxidative injury and inhibited apoptosis by increasing antioxidant enzyme activities and modifying bcl-2 expression and bax/bcl-2 ratio. The GLP extract exhibited potent antioxidant effect in vivo. The effect can contribute, at least in part, to the inhibition of apoptosis.
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PMID:HPLC analysis of Ganoderma lucidum polysaccharides and its effect on antioxidant enzymes activity and Bax, Bcl-2 expression. 1994 92

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

The present study was conducted to investigate the possible protective effects of lycopene (LP) and ellagic acid (EA) on aroclor (AR) 1254-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. The control group was treated with placebo. LP (10 mg/kg/every other day), EA (2 mg/kg/every other day) and AR (2 mg/kg/day) groups were given alone LP, EA and AR respectively. One of the last two groups received AR + LP, and the other treated with AR + EA. Body and reproductive organ weights, epididymal sperm characteristics, testicular tissue lipid peroxidation levels, antioxidant enzyme activities, histopathological changes and apoptosis via Bax and Bcl-2 genes were investigated. AR administration caused statistically significant decreases in body-weight, epididymal sperm concentration, testicular superoxide dismutase activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen's testicular score, and increases in relative weights of testis, epidydimis and seminal vesicles, rates of abnormal sperm and apoptotic cell expression along with degeneration, desquamation and disorganization in spermatogenic cells, and interstitial oedema and congestion in testicular tissue. LP and EA treatments to AR-treated rats markedly decreased abnormal sperm rates, testicular thiobarbituric acid reactive substances level, and increased the glutathione (GSH) level, GSH-peroxidase, catalase activities and epidiymal sperm concentration as compared with the alone AR group. Additionally, the AR-induced histopathological damages were totally or partially recovered by LP or EA administrations respectively. AR damages the testicular tissue and spermatozoa by impairing the oxidant/antioxidant balance and by increasing the apoptotic spermatogenic cell rates. However, both LP and EA have modulator effects on AR-induced reproductive dysfunction in male rats.
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PMID:Modulatory effects of lycopene and ellagic acid on reproductive dysfunction induced by polychlorinated biphenyl (Aroclor 1254) in male rats. 2007 68


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