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)

Free radical-mediated mechanisms of cellular damage have been implicated in the early stages of spinal cord injury (SCI). Manganese superoxide dismutase (MnSOD) is a potent scavenger of superoxide radicals and likely serves an important cytoprotective role in preventing cellular damage after SCI. We have evaluated the expression of MnSOD to address its role during the early events of SCI using a well-established rat contusion model. Northern analysis showed a rapid induction of MnSOD mRNA between 2 and 6 h post injury. Observed time-dependent increases in MnSOD message was maximal 6 h post injury over that of MnSOD mRNA levels induced by laminectomy alone. Immunoblot and immunohistochemical analysis demonstrated increased expression of MnSOD protein 24 h after SCI with localization primarily within neurons. Interestingly, laminectomy alone also caused an induction of MnSOD gene and protein expression. To evaluate one potential mechanism of MnSOD induction, we microinjected the naive spinal cord with IL-1beta, which caused a similar fold induction of MnSOD mRNA levels by 6 h as observed with SCI, thus implicating it as a potential inducer of MnSOD during SCI. In summary, these results demonstrate that this potent cytoprotective antioxidant enzyme is rapidly and significantly induced as a consequence of SCI.
J Neurotrauma 2002 Sep
PMID:Induction of manganese superoxide dismutase in acute spinal cord injury. 1248 19

The flavonol quercetin shows a wide range of effects in biological systems. We investigated whether quercetin exerts its proposed antioxidant properties via the antioxidant enzyme system. Quercetin in a concentration range from 5 to 100 microM decreased manganese superoxide dismutase, glutathione peroxidase, and copper zinc superoxide dismutase mRNA expression levels each by 30-40% in rat hepatoma H4IIE cells. Catalase mRNA expression levels increased about 30% but only with the cytotoxic concentration of 100 microM. Despite the down-regulation of antioxidant enzyme mRNA expression quercetin treatment of cells induced only a mild oxidative stress. Pretreatment of H4IIE cells with quercetin even protected against an oxidative stress resulting from hydrogen peroxide exposure. In conclusion, the antioxidant capacity of quercetin was shown not to be due to the antioxidant enzyme system.
Arch Toxicol 2003 Sep
PMID:The effect of quercetin on the mRNA expression of different antioxidant enzymes in hepatoma cells. 1275 20

This study was designed to determine the histological and metabolic effects of the administration of 5'-AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) for 14 successive days. AICAR treatment caused a significant decrease in the percentage of type IIB fibers and the concomitant increase in the percentage of type IIX fibers in extensor digitorum longus (EDL) muscle. The capillary density and the capillary-to-fiber ratio were not altered by AICAR. AICAR treatment increased the glycolytic and oxidative enzyme activities but not the antioxidant enzyme activities. The AICAR treatment increased the uncoupling protein 3 (UCP3) level in EDL and the peroxisome proliferator-activated receptor-gamma coactivator-1alpha protein level in the soleus and EDL muscles, whereas the myogenin level was not altered by AICAR. These results seem to imply that the chronic activation of AMPK alters such muscle histochemical and metabolic characteristics.
J Appl Physiol (1985) 2003 Sep
PMID:Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles. 1277 6

Copper chaperones are copper-binding proteins that directly insert copper into specific targets, preventing the accumulation of free copper ions that can be toxic to the cell. Despite considerable advances in the understanding of copper transfer from copper chaperones to their target, to date, there is no information regarding how the activity of these proteins is regulated in higher eukaryotes. The insertion of copper into the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) depends on the copper chaperone for SOD1 (CCS). We have recently reported that CCS protein is increased in tissues of rats fed copper-deficient diets suggesting that copper may regulate CCS expression. Here we show that whereas copper deficiency increased CCS protein in rats, mRNA level was unaffected. Rodent and human cell lines cultured in the presence of the specific copper chelator 2,3,2-tetraamine displayed a dose-dependent increase in CCS protein that could be reversed with the addition of copper but not iron or zinc to the cells. Switching cells from copper-deficient to copper-rich medium promoted the rapid degradation of CCS, which could be blocked by the proteosome inhibitors MG132 and lactacystin but not a cysteine protease inhibitor or inhibitors of the lysosomal degradation pathway. In addition, CCS degradation was slower in copper-deficient cells than in cells cultured in copper-rich medium. Together, these data show that copper regulates CCS expression by modulating its degradation by the 26 S proteosome and suggest a novel role for CCS in prioritizing the utilization of copper when it is scarce.
J Biol Chem 2003 Sep 12
PMID:Copper modulates the degradation of copper chaperone for Cu,Zn superoxide dismutase by the 26 S proteosome. 1283 19

Total sialic acid levels (TSA), antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) levels were investigated during the developmental period in tadpoles of the predominantly terrestrial amphibian B. viridis and the predominantly aquatic amphibian R. r. ridibunda. Maximum TSA levels were observed in B. viridis and R. r. ridibunda at the fifth and third week of their development, respectively. SOD and CAT activity variations during development in B. viridis were higher than in R. r. ridibunda. Although SOD activity in B. viridis was higher than R. r. ridibunda at the eighth week, SOD activity increased 19.2-fold in R. r. ridibunda and 10.4-fold in B. viridis between the first and eighth week. CAT activity in R. r. ridibunda did not significantly change (p>0.001) until the fifth week then increased, whereas in B. viridis CAT increased after the third week. In contrast to the rise in the antioxidant enzyme activities, LPO levels tended to decrease during the developmental period. Levels of LPO showed a similar trend until the third week for both species. The minimum LPO levels in B. viridis and R. r. ridibunda were 23+/-1.2 and 146+/-7.3 nmol MDA g(-1) tissue, at the eighth week, respectively. While decreasing LPO levels correlated with increasing antioxidant enzyme activities, TSA tended to decrease after reaching a maximum point.
Cell Biochem Funct 2003 Sep
PMID:The relationship between total sialic acid levels and antioxidant status in the tadpoles of Bufo viridis and Rana ridibunda ridibunda. 1291 Apr 79

Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous intracellular oxidoreductase system with antioxidant and redox regulatory roles. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In some human tumors, the thioredoxin system is found over-expressed. Because of its role in stimulating cancer cell growth and as an inhibitor of apoptosis, the Trx system offers a target for the development of drugs to treat and prevent cancer. In a previous research, we successfully synthesized a novel organoselenium compound BBSKE(1,2-[bis(1,2-Benzisoselenazolone-3(2H)-ketone)]ethane, BBSKE, PCT: CN02/00412) targeting the TrxR, and it has demonstrated the inhibitory effect on the growth of a variety of human cancer cells from various organs. In this study, we investigated the inhibitory effect of BBSKE on TrxR activity in PC-3 and DU145 human prostate cancer cell lines, and its antitumoral effect on these two cell lines. Treatment of BBSKE inhibited the TrxR activity in both of the cell lines in a dose-dependent manner and it also inhibited the proliferation of these two cell lines in a dose-dependent manner. Cell cycle analysis showed S phase arrest in both of the cell lines following 48 h exposure to BBSKE. During the S arrest, analysis of cell cycle regulatory proteins demonstrated that BBSKE increased the protein levels of cyclinA, cyclinE, and P21, but decreased the levels of cyclinB1, cyclinD1, and Cdk4. Furthermore, BBSKE decreased the protein level of Bcl-2 but increased the level of Bax, and induced apoptosis in PC-3 and DU145 human prostate cancer cell lines. These results suggest that this novel TrxR inhibitor inhibits the proliferation of prostate cancer cells via S phase arrest and apoptosis in association with the regulation of multiple molecules in the cell cycle.
Biochem Biophys Res Commun 2003 Sep 26
PMID:A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines. 1296 29

Long-Evans Cinnamon (LEC) rats spontaneously develop fulminant hepatitis, associated with excess Cu accumulation in the liver: thus, they are considered an animal model of Wilson's disease. In the present study, we investigated the ability of excess dietary histidine to reduce the excess accumulation of liver Cu in LEC rats by comparing them with Fischer rats. The results clearly showed that the excess-histidine diet markedly stimulated the Cu excretion in urine, and significantly decreased the liver Cu content in LEC rats by 47.5%. The serum Cu content in LEC rats was not influenced by excess dietary histidine. We also compared the effects of excess dietary histidine on some liver antioxidant enzyme activities, liver and serum lipid levels and serum alanine aminotransferase activity of LEC and Fischer rats. Dietary histidine decreased the activities of total and Cu,Zn-superoxide dismutase in the liver of both strains. In LEC rats, the liver cholesterol content decreased, and serum cholesterol and phospholipids levels increased on feeding the excess-histidine diet. When fed on the basal diet, the serum alanine aminotransferase activity was higher in LEC rats than in Fischer rats, but a significant decrease in serum alanine aminotransferase activity of LEC rats was observed on feeding the excess-histidine diet. These results suggest that excess dietary histidine is effective in removing Cu ions from the liver of LEC rats. Thus, it may be of benefit in the prevention or treatment of liver injury in LEC rats and in patients with Wilson's disease.
Br J Nutr 2003 Sep
PMID:Excess dietary histidine decreases the liver copper level and serum alanine aminotransferase activity in Long-Evans Cinnamon rats. 1312 63

This study was designed to investigate whether genistein may ameliorate oxidative stress and nuclear factor kappaB (NFkappaB) activation in the lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cell line. Treatment of RAW 264.7 cells with genistein significantly reduced lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in a dose-dependent manner with an IC50 of 69.4 microM. Genistein at 50 microM and 100 microM concentrations reduced thiobarbituric acid-reactive substances (TBARS) accumulation, increasing the GSH level and antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase. The specific DNA-binding activities of nuclear factor kappaB (NFkappaB) on nuclear extracts from 50 microM and 100 microM genistein treatments were significantly suppressed. These results suggest that genistein has mild antioxidant activity to suppress intracellular oxidative stress and NFkappaB activation.
Biosci Biotechnol Biochem 2003 Sep
PMID:Suppressive effects of genistein on oxidative stress and NFkappaB activation in RAW 264.7 macrophages. 1451 76

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.
Cancer Res 2003 Sep 15
PMID:Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide. 1452 20

Although cutaneous leishmaniasis (CL) is a local infection, the cellular immune response against the disease is systemic, and reactive oxygen intermediates (ROIs) are an important part of cellular immune response involved in killing the parasite. However, whether these intermediates cause oxidative damage in host is unknown. In this study, the metabolism of ROIs were investigated in patients with CL, and compared with healthy subjects. Erythrocyte lipid peroxidation was determined, as an index of oxidative damage, by measurement of malondialdehyde (MDA) levels. Erythrocyte MDA levels and SOD activities were found to be significantly higher in CL patients than in control subjects (p < 0.01 and p < 0.01, respectively). However, CAT and GSH-Px activities were significantly lower in the CL group (p < 0.05 and p < 0.01, respectively). There was a tendency to decreased hemoglobin (Hb) levels, but values did not reach statistical significance. These findings suggest that changes in antioxidant enzyme activities may amplify the leishmanicidal effect in patients with CL. However, these changes may not only cause the killing of parasite but also may cause oxidative damage in the other cells or tissues.
Parasite 2003 Sep
PMID:Erythrocyte antioxidative enzyme activities and lipid peroxidation levels in patients with cutaneous leishmaniasis. 1453 69


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