Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exploratory studies were undertaken to ascertain the role of pro/antioxidative processes during a 3 weeks administration of low sub-toxic dose of diazepam and its withdrawal. Rats were administered 3 mg/kg diazepam for 21 consecutive days and the changes observed in different regions of rat brain at the sub-cellular level. Mitochondria from cerebrum showed a 27% lowering of TBARS whereas those from cerebellum and brain stem showed 48 and 24% enhanced MDA levels respectively. No significant alteration in the SOD isozymes was observed after the dose schedule. The mitochondrial glutathione reductase (GR) activity showed a decrease in all the regions with maximum decrease (36%) recorded in brain stem while post mitochondrial fraction showed significant lowering in cerebrum (37%). Total -SH content increased in all the three regions with maximum enhancement recorded in cerebellum while the free thiol content also showed significant changes (p < 0.001) in cerebellum and brain stem. One week after the withdrawal of the drug MDA levels decreased by 38% in cerebrum and 53% each in mitochondrial fractions of cerebellum and brain stem. Regional heterogeneity in response was also observed in the post mitochondrial fractions. Mn-SOD showed lowered activity in cerebellum (22%) and in brain stem (15%). The mitochondrial GR activity decreased in all the regions being highest in cerebrum with no significant change in post mitochondrial fractions. The total and free -SH content in the withdrawn animals increased by 46% in cerebellum with no change in the other two regions. The results indicate towards lower oxidative phenomenon during 3 weeks treatment with diazepam while abrupt withdrawal causes lowering of antioxidant defenses which showed regional heterogeneity. A decrease in peroxidative decomposition of polyunsaturated fatty acids of membranes was observed on withdrawal, which could be due to stabilisation of membranes after long-term binding of diazepam.
Mol Cell Biochem 2003 Mar
PMID:Effect of diazepam treatment and its withdrawal on pro/antioxidative processes in rat brain. 1270 44

To identify molecular events occurring during the early response to hyperoxia, we measured changes over time in total lung gene expression in C57BL/6 mice during prolonged exposure to > 95% O2. Specifically, differential gene expression of > 8,734 sequence-verified murine complementary DNAs was analyzed after 0, 8, 24, and 48 h of O2 exposure, with additional genes of interest analyzed at 24 h. Of the 385 genes differentially expressed, hyperoxia increased expression of 175 genes (2.0%) and decreased expression of 210 genes (2.3%). The majority of "classic" antioxidant enzymes, including catalase, MnSOD, and Cu-Zn SOD, showed no change in expression during hyperoxia, with a number of other antioxidant enzymes, including glutathione peroxidase, glutathione-S-Transferase (GST) Pi1, GST mu2, and heme oxygenase-1 showing relatively moderate increases. The exception was the heavy metal-binding protein metallothionein, which increased expression over 7-fold after 48 h of O2. We found no change in the expression of a number of known proinflammatory genes after 24 or 48 h of hyperoxia. A large increase in p21 expression was demonstrated, suggesting overall inhibition of cell cycle progression. Increases of the antiapoptotic gene Bcl-XL were counterbalanced by similar increases of the proapoptotic gene BAX. New findings included significant increases in expression of cysteine-rich protein 61(cyr61) at 48 h, suggesting a potential role for this factor in angiogenesis or remodeling of the extra cellular matrix during recovery from hyperoxia. In addition, downregulation of thrombomodulin expression occurred by 24 h and was further decreased at 48 h. Given the importance of thrombomodulin/thrombin interaction in regulating protein C activity, decreases in thrombomodulin may contribute to activation of the coagulation and inflammatory cascades and development of lung injury with hyperoxia.
Am J Respir Cell Mol Biol 2003 Jun
PMID:Gene expression profiling of the early pulmonary response to hyperoxia in mice. 1276 Sep 66

The production of superoxide dismutase (SOD) varied in Deinococcus radiophilus, the UV resistant bacterium, depending upon different phases of growth, UV irradiation, and superoxide treatment. A gradual increase in total SOD activity occurred up to the stationary phases. The electrophoretic resolution of the SOD in cell extracts of D. radiophilus at each growth phase revealed the occurrence of MnSOD throughout the growth phases. The SOD profiles of D. radiophilus at the exponential phase received oxidative stress by the potassium superoxide treatment or UV irradiation also revealed the occurrence of a single SOD. However, these treatments caused an increase in SOD activity. The data strongly suggest that D. radiophilus has only one species of SOD as a constitutive enzyme, which seems to be a membrane-associated protein.
J Biochem Mol Biol 2003 May 31
PMID:Production of superoxide dismutase by Deinococcus radiophilus. 1278 83

In the cyclic cow, final maturation of the ovulatory follicle is initiated by the preovulatory luteinizing hormone (LH) surge. During the subsequent 24 hr period, the oocyte nucleus undergoes meiotic progression to metaphase II and several changes in cytoplasmic organization take place. We have previously shown that oocytes recovered at the time of the LH peak and matured in vitro are less competent to reach the blastocyst stage than their counterparts recovered 20 hr later following in vivo maturation, despite both groups undergoing IVF and culture in parallel. The objective of this study was to compare, using real-time quantitative RT-PCR, the relative abundance of various developmentally important gene transcripts in these oocytes. The groups used were mature bovine oocytes originating from: (1) 2-6 mm follicles from slaughterhouse ovaries; (2) preovulatory follicles punctured by ovum pick-up just before the LH surge (i.e., immature) and matured in vitro; or (3) preovulatory follicles punctured 20 hr later, just prior to ovulation (i.e., in vivo matured). In addition, immature oocytes from 2-6 mm follicles were examined. We examined the relative mRNA expression of five enzymes involved in protection against free oxygen radicals (mitochondrial Mn-superoxide dismutase, MnSOD, cytosolic Cu/Zn superoxide dismutase, Cu/ZnSOD, gamma-glutamyl-cysteine transferase, GCS, glutathione peroxidase, GPX, sarcosine oxidase, SOX), a transcript involved in follicular development (growth differentiation factor-9, GDF-9), transcripts involved in glucose metabolism (glucose-6-phosphate dehydrogenase, G6PDH, glucose transporter type-1 and -8, Glut-1, Glut-8) and genes involved in cell cycle events, Cyclin A and B, and poly(A) polymerase (PAP). Transcripts for all genes were detected, irrespective of oocyte origin. While differences were not significant in all cases, variations in levels of transcript abundance between the groups were related to developmental competence. In particular, transcripts for GDF-9 were expressed at significantly higher levels in oocytes recovered at the LH peak and matured in vitro than in those matured in vivo. The observations with GDF-9 are interesting as this gene is believed to be essential for normal folliculogenesis and may be important in the regulation of early follicle and oocyte growth. In conclusion, the results of this study demonstrate differences in the relative mRNA abundance of several developmentally important gene transcripts in bovine oocytes which may be related to developmental competence.
Mol Reprod Dev 2003 Nov
PMID:Relative messenger RNA abundance in bovine oocytes collected in vitro or in vivo before and 20 hr after the preovulatory luteinizing hormone surge. 1450 9

Reactive oxygen species (ROS) cause macromolecular damage and may play an important role in tumor development. Superoxide dismutase (SOD) and metallothionein (MT) serve as initial and final defense mechanisms, respectively, against ROS. We hypothesized that the inducibility of Mn-SOD and MT mRNA by paraquat, an intracellular superoxide generator, might be altered in lymphocytes of gastric cancer patients. The inducibility of Mn-SOD mRNA by paraquat in lymphocytes of 19 normal subjects and the 14 gastric cancer patients was 162.4 +/- 16.7% and 87.9 +/- 9.5%, respectively (P = 0.001). The inducibility of MT mRNA by paraquat in the normal subjects and the gastric cancer patients was 126.7 +/- 15.8% and 115.4 +/- 12.9%, respectively. This suggests that the failure of Mn-SOD mRNA induction by oxidative stress in peripheral lymphocytes may be involved in the development of gastric cancer and may be of value in predicting the future occurrence of gastric cancer. In addition, the wide variation in Mn-SOD and MT mRNA levels among normal subjects may reflect different susceptibilities to diseases including cancer.
Mol Cells 2003 Aug 31
PMID:Differential induction of Mn-containing superoxide dismutase by paraquat in peripheral lymphocytes of normal subjects and gastric cancer patients. 1450 39

SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn super-oxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2)were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of upstream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.
Cell Mol Life Sci 2003 Aug
PMID:Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells. 1451 38

In this work, the topology of mitochondrial O2(-)(radical) and H2O2 generation and their interplay with matrix GSH in isolated heart mitochondria were examined. We observed that complex I releases O2(-)(radical) into the matrix (where it is converted to H2O2 by Mn-SOD) but not into the intermembrane space. No free radical generation was observed from complex II, but succinate treatment caused H2O2 generation from the matrix through a reverse electron flow to complex I. Complex III was found to release O2(-)(radical) into the matrix and into the intermembrane space. Antimycin, which increases steady-state levels of UQO>- (ubisemiquinone at the Qo site) in complex III, enhanced both H2O2 generation from the matrix and O2(-)(radical) production from the intermembrane space. On the other hand, myxothiazol, which inhibits UQO>- formation, completely inhibited antimycin induced O2(-)(radical) toward the intermembrane space and inhibited H2O2 generation from the matrix by 70%. However, myxothiazol alone enhanced H2O2 production from complex III, suggesting that other components of complex III besides the UQO- can cause O2(-)(radical) generation toward the matrix. As expected, mitochondrial GSH was found to modulate H2O2 production from the matrix but not O2- generation from the intermembrane space. Low levels of GSH depletion (from 0-40%, depending on the rate of H2O2 production) had no effect on H2O2 diffusion from mitochondria. Once this GSH depletion threshold was reached, GSH loss corresponded to a linear increase in H2O2 production by mitochondria. The impact of 50% mitochondrial GSH depletion, as seen in certain pathological conditions in vivo, on H2O2 production by mitochondria depends on the metabolic state of mitochondria, which governs its rate of H2O2 production. The greater the rate of H2O2 generation the greater the effect 50% GSH depletion had on enhancing H2O2 production.
Mol Pharmacol 2003 Nov
PMID:Effect of glutathione depletion on sites and topology of superoxide and hydrogen peroxide production in mitochondria. 1457 63

Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time.
Mol Cell Biochem 2003 Sep
PMID:Antioxidant enzyme gene expression in congestive heart failure following myocardial infarction. 1457 98

Superoxide dismutases (SOD) convert superoxide radicals into less damaging hydrogen peroxide. The opportunistic human pathogen Candida albicans is known to express CuZnSOD (SOD1) and MnSOD (SOD3) in the cytosol and MnSOD (SOD2) in the mitochondria. We identified three additional CuZn-containing superoxide dismutases, SOD4, SOD5, and SOD6, within the sequence of the C. albicans genome. The transcription of SOD5 was up-regulated during the yeast to hyphal transition of C. albicans, and SOD5 was induced when C. albicans cells were challenged with osmotic or with oxidative stresses. SOD5 transcription was also increased when cells were grown on nonfermentable substrates as the only carbon source. The Rim101p transcription factor was required for all inductions observed, whereas the Efg1p transcription factor was specifically needed for serum-modulated expression. Deletion of SOD5 produced a viable mutant strain that showed sensitivity to hydrogen peroxide when cells were grown in nutrient-limited conditions. Sod5p was found to be necessary for the virulence of C. albicans in a mouse model of infection. However, the sod5 mutant strain showed the same resistance to macrophage attack as its parental strain, suggesting that the loss of virulence in not due to an increased sensitivity to macrophage attack.
Mol Biol Cell 2004 Feb
PMID:Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene. 1461 19

The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are very poorly understood. To investigate the effect of endurance training on the expression of various genes at the mRNA levels in human skeletal muscle, focusing on angiogeneic factors, antioxidant enzymes, and uncoupling proteins (UCPs), seven untrained male students underwent an intensive swimming training five times a week for 3 months and two male students an intensive running training, respectively. Muscle biopsies were taken before training and about 48 h after the last session. All the subjects markedly increased their maximal oxygen uptake levels due to training (P < 0.001), indicating an improvement in aerobic capacity. After training, there were significant (P < 0.04) decreases in the expression of mRNAs for heat shock protein 70, Cu,Zn-superoxide dismutase (Cu,Zn-SOD), and Mn-SOD but a significant (P < 0.02) increase in UCP2 mRNA expression, whereas no definite changes were observed in the levels of mRNAs for vascular endothelial growth factor (VEGF), basic fibroblast growth factor, hypoxia-inducible factor-1alpha (HIF1alpha), myoglobin, or UCP3. The changes in HIF1alpha mRNA expression correlated well with those in VEGF mRNA expression after training (r=0.875, P < 0.01), suggesting that HIF1alpha influences the training-induced VEGF gene expression or alternatively that VEGF and HIF1alpha expressions are coregulated at the transcriptional level in human skeletal muscle. Taken together, it is envisioned that cumulative effects of transient changes in transcription during recovery from successive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with endurance training.
Res Commun Mol Pathol Pharmacol 2002
PMID:Transcription regulation of gene expression in human skeletal muscle in response to endurance training. 1463 13


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