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)

Quorum sensing (QS) governs the production of virulence factors and the architecture and sodium dodecyl sulphate (SDS) resistance of biofilm-grown Pseudomonas aeruginosa. P. aeruginosa QS requires two transcriptional activator proteins known as LasR and RhlR and their cognate autoinducers PAI-1 (N-(3-oxododecanoyl)-L-homoserine lactone) and PAI-2 (N-butyryl-L-homoserine lactone) respectively. This study provides evidence of QS control of genes essential for relieving oxidative stress. Mutants devoid of one or both autoinducers were more sensitive to hydrogen peroxide and phenazine methosulphate, and some PAI mutant strains also demonstrated decreased expression of two superoxide dismutases (SODs), Mn-SOD and Fe-SOD, and the major catalase, KatA. The expression of sodA (encoding Mn-SOD) was particularly dependent on PAI-1, whereas the influence of autoinducers on Fe-SOD and KatA levels was also apparent but not to the degree observed with Mn-SOD. beta-Galactosidase reporter fusion results were in agreement with these findings. Also, the addition of both PAIs to suspensions of the PAI-1/2-deficient double mutant partially restored KatA activity, while the addition of PAI-1 only was sufficient for full restoration of Mn-SOD activity. In biofilm studies, catalase activity in wild-type bacteria was significantly reduced relative to planktonic bacteria; catalase activity in the PAI mutants was reduced even further and consistent with relative differences observed between each strain grown planktonically. While wild-type and mutant biofilms contained less catalase activity, they were more resistant to hydrogen peroxide treatment than their respective planktonic counterparts. Also, while catalase was implicated as an important factor in biofilm resistance to hydrogen peroxide insult, other unknown factors seemed potentially important, as PAI mutant biofilm sensitivity appeared not to be incrementally correlated to catalase levels.
Mol Microbiol 1999 Dec
PMID:Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. 1059 32

Superoxide dismutase (SOD) protects cells exposed to an excess of the free radical nitric oxide, by preventing the formation of peroxynitrite. Certain central cholinergic neurons express constitutive nitric oxide synthase (nNOS), and presumably they are at risk from peroxynitrite intoxication. Immunocytochemistry for choline acetyltransferase (ChAT) was combined with in situ hybridization histochemistry (ISHH) to examine whether brain cholinergic populations differ with respect to their expression of the messenger RNA molecules (mRNAs) for the manganese-dependent (Mn-SOD) and copper/zinc-dependent superoxide dismutases (Cu /Zn-SOD). The cholinergic neurons located in the reticular formation of the upper brainstem (the laterodorsal tegmental nucleus [LDTN] and the pedunculopontine nucleus [PPN]) were found to express relatively high levels of Mn-SOD mRNA, whereas cholinergic neurons located in the basal forebrain (substantia innominata [SI], diagonal band [DB], medial septum [MS], and the nucleus basalis magnocellularis [nBM]), and the striatal cholinergic interneurons expressed low to intermediate levels of Mn-SOD mRNA. The rank order of median Mn-SOD mRNA density per cholinergic cell was LDTN > PPN > SI > striatum = nBM = DB > MS. This is similar to the rank order of nNOS mRNA densities in the cholinergic cells in these regions (R = 0.9, p < 0.02). The rank order of Cu/Zn-SOD mRNA levels in cholinergic populations (DB > LDTN = PPN =MS > SI = nBM = striatum) was not correlated with nNOS mRNA (R = 0.29, P > 0.05). Thus, for cholinergic neurons, Mn-SOD may be important for protection from NO-related oxidative stress.
J Mol Neurosci 1999 Feb
PMID:Expression of superoxide dismutase messenger RNA in adult rat brain cholinergic neurons. 1063 66

It is well known that ICAM-1 expression can be stimulated by TNF and by oxidative stress, via the activation of specific transcription factors. Two of these--NFkappaB and AP-1--can also be activated by reactive oxygen species, including the superoxide anion (also produced under TNF challenge). The latter is inactivated by superoxide dismutase of which two forms exist: Cu/Zn-SOD (cytoplasmic) and Mn-SOD (mitochondrial). We investigated whether superoxide anion direct generation or accumulation through specific SOD inhibition, may affect ICAM-1 expression in human melanoma and endothelial cells. Our results show a 20-50% increase in both SOD activities when cells were exposed to TNF or to an oxidative stress produced by Paraquat (a generator of superoxide anion radicals), both in terms of enzymes activity (zymogram) and protein levels (Western blotting and ELISA). Either with TNF or Paraquat, we could measure a significant increase of ICAM-1 expression with maxima ranging from 140 to 200%, depending on the cell line. Specific inhibition of Cu/Zn-SOD activity by DTIC (diethyldithiocarbamic acid), in presence of Paraquat or TNF, was followed by an upregulation of ICAM-1 expression (60 and 20%, respectively). In contrast, the addition of a SOD mimetic (MnTMPyP) completely inhibited Paraquat-stimulated ICAM-1 expression in melanoma cells and significantly decreased it in HUVEC (50%). In presence of TNF however, the same SOD mimetic inhibited TNF-stimulated ICAM-1 expression by 25% in melanoma and 17% in endothelial cells. In conclusion, these data provide evidence that melanoma and endothelial cells exposure to TNF or oxidative stress results in a significant increase of both Mn- and Cu/Zn-SOD activities. This increase seems to be associated with a reduction in the stimulation of ICAM-1 expression by TNF or oxidative stress.
Cell Mol Biol (Noisy-le-grand) 1999 Nov
PMID:SODs are involved in the regulation of ICAM-1 expression in human melanoma and endothelial cells. 1064 10

The present study investigates intracellular enzymatic pathways involved in the elimination of reactive oxygen species in the left ventricular myocardium of 10 individuals without heart failure and 12 patients with end-stage heart failure due to idiopathic dilated cardiomyopathy. Left ventricular enzyme activities, mRNA and protein levels of the hydrogen peroxide scavenging enzymes catalase (CAT) and glutathione peroxidase (GPX), and the superoxide anion scavenging enzymes mitochondrial (Mn-SOD) and cytosolic (Cu/Zn-SOD) superoxide dismutases were measured. In failing myocardium, there was a significant decrease in CAT activity (4.83+/-0.32 U/mg v 6.59+/-0.52, P<0.01) despite unchanged mRNA expression and protein levels. GPX, Mn-SOD and Cu/Zn-SOD were similar concerning activity, mRNA and protein levels. As indirect free radical markers, similar levels of the products of lipid peroxidation, malondialdehyde and 4-hydroxy-alkenals, and similar tissue nitrotyrosin content were measured. The decrease in CAT activity appears to be a post-transcriptional mechanism. A decreased myocardial capacity to scavenge hydrogen peroxide might lead to a shift in the intracellular redox balance which potentially results in activation of redox sensitive signalling pathways. Direct reactive oxygen species mediated damage was not detected by the methods applied.
J Mol Cell Cardiol 2000 Jan
PMID:Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy. 1065 96

The present study was undertaken to investigate the effect of decidualization on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC). To induce decidualization, isolated ESC were incubated with medroxyprogesterone acetate (MPA, 10(-6) mol/l) and oestradiol (10(-8) mol/l) for 23 days. Insulin-like growth factor-binding protein-1 (IGFBP-1) was used as a marker of decidualization. SOD mRNA in ESC was significantly increased on day 12 of the hormone treatment (P < 0.01), which was concomitant with the onset of IGFBP-1 mRNA expression, and further increased until day 23 of the treatment in a manner similar to the change in IGFBP-1 expression. To examine the synergistic effect of human chorionic gonadotrophin (HCG) with MPA and oestradiol on SOD and IGFBP-1 expression, ESC were incubated with HCG in the presence or absence of MPA and oestradiol. HCG had no synergistic effect on SOD and IGFBP-1 expression. SOD activities in the decidualized endometrial tissue obtained from patients given oestradiol and progesterone for 7-10 days were significantly higher than those in the non-decidualized endometrial tissue from patients without the hormone treatment (P < 0.01). In conclusion, SOD expression in ESC was induced by MPA and oestradiol accompanied by decidualization, suggesting that SOD may play important roles in decidualization of ESC.
Mol Hum Reprod 2000 Feb
PMID:Induction of superoxide dismutase by decidualization in human endometrial stromal cells. 1065 60

The study was designed to demonstrate--for the first time in humans--that oxidative stress in the heart indicated by lipid peroxidation is associated with time-dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial biopsies (taken between the fifth day and 6 years after transplantation) of 31 heart transplant recipients who were suspected of suffering from increased formation of oxygen radicals in the allograft. The levels of lipid peroxides (LPO), glutathione peroxidase (GSH-Px), total-, copper/zinc- and manganese superoxide dismutase (t-SOD, CuZnSOD, MnSOD) were compared in 3 post-transplantation periods (5-90 d vs. 91-365 d vs. >1 y). Significantly increased LPO levels were found (0.27+/-0.04 vs. 0. 13+/-0.02 vs. 0.27+/-0.04 nmol/mg protein) in the first and third period. Increased activities of GSH-Px (39.8+/-3.8 vs. 30.2+/-4.1 vs. 76.7+/-6.5 mU/mg protein), t-SOD (1.57+/-0.10 vs. 1.30+/-0.14 vs. 2.44+/-0.23 U/mg protein) and CuZnSOD (1.09+/-0.08 vs. 0.93+/-0.13 vs. 2.05+/-0.21 U/mg protein) occurred only in the third period. For calculation of time courses more precisely, the single data with respect to time were analyzed with a curve fitting program. Except for the first period, the allograft LPO and GSH-Px levels rose for up to 6 years after transplantation. However, the t-SOD and CuZnSOD activities switched from increase to decrease in the third period. The study provided indication for: first, the potency of the human heart to time-limited increase of the enzymatic antioxidative defense, and secondly, the inability of human heart allografts--despite this adaptation--for complete prevention of myocardial oxidative stress.
Mol Cell Biochem 2000 Jan
PMID:Oxidative stress in the human heart is associated with changes in the antioxidative defense as shown after heart transplantation. 1071 29

Reactive oxygen species (ROS; O2-, H2O2, and OH), normal by-products of cellular metabolic processes, are kept in control by antioxidant enzymes, such as catalase, glutathione peroxidase (GPX) and superoxide dismutases (SODs). To understand the role of antioxidant enzymatic defenses against ROS injury following ischemia-reperfusion, we examined the effect on kidney exposed to varying periods (30, 60 or 90 min) of ischemia followed by different periods of reperfusion. The enzymatic activities and protein levels of catalase, GPX, CuZnSOD and MnSOD were relatively unaffected at 30 min of ischemia followed by 0, 2 or 24 h reperfusion. However, 60 or 90 min of ischemia followed by 0, 2 or 24 h of reperfusion resulted in a decrease in activities and protein levels which paralleled the duration of ischemic injury. MnSOD activity tended to recover towards normal during reperfusion. Examination of the mRNA levels of these antioxidant enzymes demonstrated a severe decrease in mRNA levels of catalase and GPX at a time point of minimal ischemic injury (30 min of ischemia followed by reperfusion) suggesting that loss of mRNA of catalase and GPX may be the first markers of alterations in cellular redox in ischemia-reperfusion injury. Greater loss of mRNA for catalase, GPX and CuZnSOD was observed following longer periods (60 or 90 min) of ischemia. The mRNA for MnSOD was upregulated at all time points of ischemia-reperfusion injury. Actually, the greater decrease in mRNAs for catalase, GPX and CuZnSOD in the acute phase (within 24 h) subsequently showed a further decrease in these enzyme activities in the subacute phase (72 or 120 h after ischemia). These enzyme activities in the 30 min ischemia group, (but not in the 90 min group), already showed tendencies for normalization at 120 h after ischemia. To understand the molecular basis of the loss of mRNA of these antioxidant enzymes during ischemia-reperfusion injury, we examined the rate of transcription by nuclear run-on assays. The similar rates of transcription in control and kidney exposed to ischemia-reperfusion indicates that the loss of mRNA for catalase, GPX and CuZnSOD is possibly due to the increased rate of turnover of their mRNAs. These studies suggest that expression of antioxidant genes during ischemia-reperfusion are not coordinately expressed and that the differential loss of antioxidant enzymes may be the contributing factor(s) towards the heterogeneous renal tissue damage as a result of ischemia-reperfusion induced oxidative stress.
Mol Cell Biochem 2000 Feb
PMID:Kidney ischemia-reperfusion: modulation of antioxidant defenses. 1082 17

The mechanism(s) of the "aldosterone turn-off phenomenon", hypoaldosteronemia following chronic ACTH administration, remains unclear. Our previous observation that antioxidants prevented turn-off prompted us to evaluate the chronic effect of ACTH on the enzymatic antioxidant system as well as P450aldo activity and expression of CYP11B2 in adrenal zona glomerulosa. Male Wistar rats were administered ACTH-Z for 5 days with or without antioxidants, vitamin E or DMSO. Adrenal capsules were prepared for P450aldo activity measurement and mRNA content determination by competitive RT-PCR, and immunoreactivity of Mn-SOD in whole adrenals was evaluated. ACTH decreased the P450aldo activity and mRNA level of CYP11B2 in adrenal capsules, while co-administration of vitamin E or DMSO partially blocked this inhibition. ACTH increased Mn-SOD mRNA and immunoreactivity but decreased GPx mRNA. These results suggest that prolonged ACTH treatment increases oxidative stress in the zona glomerulosa and an imbalance in the ratio of Mn-SOD to GPx, possibly via corticosterone overproduction in the zona fasciculata, resulting in the downregulation of CYP11B2. Vitamin E and DMSO might thus protect CYP11B2 expression through their antioxidant actions.
J Steroid Biochem Mol Biol 2000 May
PMID:Role of rat adrenal antioxidant defense systems in the aldosterone turn-off phenomenon. 1082 27

The role of pro/antioxidative processes during a low, subtoxic dose schedule of diazepam (3 mg/kg/day i.p.) for 7 days and its withdrawal in subcellular preparations of rat brain regions was studied in detail. The results indicated heterogeneity in the regional responses as well as in subcellular compartments. After 7 days of exposure to the drug, a decrease in the Mn-SOD activity was observed in the 3 regions studied while a significant increase in Cu/Zn-SOD activity was seen in cerebellum (CBL) and brain stem (BS) along with that of mitochondrial glutathione reductase. The post-mitochondrial fraction (PMF) showed a significant increase in GR activity in cerebrum. Enhancement of total and free thiol levels was observed in cerebrum and cerebellum whereas in BS free thiols were not enhanced. It was interesting to note that in the animals withdrawn from the drug and sacrificed after an interval of 7 days, the level of TBARS showed a highly significant increase in mitochondria of CB and CBL and 89% increase in BS. Similar trend was observed in the post-mitochondrial fractions of all the 3 regions whereas the activity of isozymes of SOD decreased (p < 0.001) in CBL and BS and to a lesser extent in CB. The GR activity was significantly decreased only in the mitochondria of cerebrum with a 34% rise in cerebellum and no change in BS. The PMFs showed a decrease in CB and CBL but a 20% rise in BS. Thus, the data show modulation of antioxidant responses during short-term administration of diazepam, and a lowering of peroxidative decomposition of polyunsaturated fatty acids of membranes. However, after withdrawal of the drug, PUFAs were found to be more vulnerable to peroxidative decomposition and changes in the antioxidant defenses were also observed, which did not come back to normal level during the study.
Mol Cell Biochem 2000 Mar
PMID:Pro and antioxidant responses to repeated administration of diazepam in rat brain. 1083 99

To study the possible role of the superoxide radical and its scavenging system in the decidua of early pregnancy, superoxide dismutase (SOD) values and concentrations of lipid peroxide and prostaglandin F(2alpha) (PGF(2alpha)) were analysed in the decidua obtained from normal pregnancy and failed pregnancy. Failed pregnancy was divided into two groups; spontaneous abortion with or without vaginal bleeding. In the spontaneous abortion with vaginal bleeding, total SOD activities, Cu,Zn-SOD activities and Cu,Zn-SOD mRNA values in the decidua were significantly lower, and concentrations of lipid peroxide and PGF(2alpha) were significantly higher, than those in the normal pregnancy and the spontaneous abortion without vaginal bleeding. In contrast, activities and mRNA values of Mn-SOD were significantly higher in the spontaneous abortion with vaginal bleeding than the other two groups. There was no significant difference in all of these parameters between the normal pregnancy and the spontaneous abortion without vaginal bleeding. In conclusion, the decrease in Cu,Zn-SOD expression and the increase in lipid peroxide in the decidua could be involved in the termination of spontaneous abortion, mediated through the increase in PGF(2alpha) synthesis. In other words, Cu,Zn-SOD may contribute to the maintenance of pregnancy by preventing the accumulation of superoxide radicals that cause PGF(2alpha) synthesis.
Mol Hum Reprod 2000 Jul
PMID:Decreased superoxide dismutase expression and increased concentrations of lipid peroxide and prostaglandin F(2alpha) in the decidua of failed pregnancy. 1087 52


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