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)

The role of lipid peroxidation and endogenous oxygen-derived free radical scavengers on ischemia-reperfusion injury and tissue recovery in rat ulcer model corresponding to the gastric histopathology was investigated. Male Wistar rats weighting 200-250 g were heparinized before occlusion of the celiac axis for 1.5 h. Endogenous CuZn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase, fumarase, cytochrome c oxidase, and thiobarbituric acid-reactive compounds as lipid peroxidation products were measured in the gastric tissue at 3 h, and 1, 2, 4, and 7 days after release and in the controls (no occlusion). At 3 h after release, erosion of the gastric mucosa was observed, and gastric ulcers beyond the muscularis mucosae were present in the gastric body 2 days later. Seven days after release, gastric ulcers had disappeared. Activity levels for all five enzymes (CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase) were low for days 1-4 after release and did not return to control levels by the seventh day. It was observed that the ulcer formation, as evidenced by the histopathology, was significantly related to the levels of endogenous CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase activities. Thiobarbituric acid-reactive compounds were also low through the entire course of ulcer formation. The study concludes that decreases in the levels of these oxygen-derived free radical scavengers may result in the formation of gastric ulcers; however, endogenous free-radical scavengers may not correspond with tissue recovery. Lipid peroxidation may not be related to ulcer formation.
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PMID:The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model. 217 May

1. A number of dietary sugars are known to mediate the effects of copper deficiency. The effects of lactose (compared with sucrose) and a dietary Cu deficiency on hepatic and cardiac antioxidant enzyme activities and tissue mineral element status were investigated in the rat. 2. Groups (n 6) of male weanling Wistar rats were provided ad lib. with deionized water and diets containing sucrose (580 g/kg) or sucrose and lactose (387 g/kg and 193 g/kg respectively) with either control (12.0 mg/kg) or deficient (1.5 mg/kg) quantities of Cu for 77 d. 3. Animals consuming the low-Cu diets exhibited significantly decreased tissue Cu levels (P less than 0.01), hepatic and cardiac cytochrome c oxidase (EC 1.9.3.1, CCO) activities (P less than 0.01 and P less than 0.001 respectively) and hepatic Cu-zinc superoxide dismutase (EC 1.15.1.1, CuZnSOD) activity (P less than 0.05). The low-Cu diets also significantly decreased cardiac manganese superoxide dismutase (EC 1.15.1.1, MnSOD), catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9, GSH-Px) activities (P less than 0.01, P less than 0.05 and P less than 0.001 respectively). 4. Hepatic Mn was significantly increased in both lactose-fed (P less than 0.001) and Cu-deficient (P less than 0.01) animals. These increases were unrelated to hepatic MnSOD activity. Cardiac Zn was significantly (P less than 0.01) increased in Cu-deficient animals. 5. Lactose feeding resulted in significantly increased cardiac CCO activity (P less than 0.001) but significantly decreased hepatic CuZnSOD (P less than 0.05), catalase (P less than 0.01) and GSH-Px (P less than 0.001) activities. 6. The activities of lactose dehydrogenase (EC 1.1.1.27, LDH) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PDH) were found to be significantly (P less than 0.05 and P less than 0.01 respectively) increased in Cu-deficient animals and G6PDH activity was significantly (P less than 0.01) decreased as a result of lactose consumption. 7. The observed changes in antioxidant enzyme activities associated with both Cu deficieny and lactose consumption may have important implications for the development of free radical mediated cell damage. However, no significant differences in either hepatic or cardiac levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation, were found.
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PMID:Effects of copper deficiency on hepatic and cardiac antioxidant enzyme activities in lactose- and sucrose-fed rats. 253 51

A sensitive and reliable assay method was developed to characterize crude cell homogenates and subcellular fractions with regard to their superoxide dismutase (SOD) activities. The determination of SOD activities was based on the well-known spectrophotometric assay introduced by McCord & Fridovich [(1969) J. Biol. Chem. 244, 6049-6055], with partially succinylated (3-carboxypropionylated) rather than native ferricytochrome c as indicating scavenger. Partial succinylation of cytochrome c resulted in minimization of interference associated with the interaction of cytochrome c with mitochondrial cytochrome c oxidase or cytochrome c reductases. The further increase in specificity, with regard to exclusion of cytochrome c oxidase interference, gained as a consequence of the high pH of 10 enabled the analysis of samples as rich in cytochrome c oxidase activity as the mitochondrial fraction in the presence or absence of membrane-disrupting detergents. Linear relationships for the dependence of the SOD activities with protein concentration were obtained with rat liver homogenate, mitochondrial and microsomal fractions, indicating negligible interference. Furthermore, by choosing a high pH for the assay medium, a 4-fold increase in sensitivity compared with the classical SOD assay, carried out at pH 7.8, was gained as well as a more precise resolution of Cu/Zn-SOD and Mn-SOD by 2 mM-KCN in samples with a high ratio of Mn-SOD to Cu/Zn-SOD, such as mitochondria. The complete trapping of the O2.- radicals, which was more feasible at pH 10 than at pH 7.8, enabled the application of a simple equation derived for the calculation of appropriately defined units of SOD activity from a single experiment.
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PMID:A spectrophotometric assay for superoxide dismutase activities in crude tissue fractions. 302 8

Immunohistochemical analyses were made of the superoxide dismutases (Mn-SOD and Cu/Zn-SOD) in biopsied muscles from 7 patients with mitochondrial encephalomyopathies that included mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), and chronic progressive external ophthalmoplegia (CPEO). Mn-SOD mainly was present in the subsarcolemmal region, but it also was found in a coarsely granular, reticular, or diffuse pattern of staining within the muscle fibers. These Mn-SOD-positive fibers corresponded almost completely to the ragged-red fibers. The immunoreaction for Cu/Zn-SOD was weakly positive in some of the muscle fibers positive for Mn-SOD. In CPEO, Mn-SOD-positive fibers predominantly showed decreased cytochrome c oxidase (COX) activity. In MELAS, Mn-SOD-positive fibers tended to be stained deeply for COX although a few were COX-negative. These findings suggest that Mn-SOD-positive fibers can be used to make a differential diagnosis between CPEO and MELAS and that in mitochondrial encephalomyopathies Mn-SOD in the ragged-red fibers may protect against oxidative stress.
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PMID:Superoxide dismutases of muscle in mitochondrial encephalomyopathies. 756 23

Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease of sheep and other animals. Clinical symptoms of prion diseases are characterized by a long latent period, followed by progressive ataxia, tremor, and death. To study the induction of neurodegeneration during scrapie infection, we have analyzed the activities of various antioxidant enzymes and mitochondrial enzymes in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected brains. The activities of glutathione peroxidase and glutathione reductase were increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might result in increasing oxidative stress in the mitochondria of infected brain; this concept is supported by our findings of a high level of lipid peroxidation, and low levels of ATPase and cytochrome c oxidase activity in the infected cerebral mitochondria. In addition, structural abnormalities of mitochondria have been observed in the neurons of hippocampus and cerebral cortex of infected brain. These results suggest that mitochondrial dysfunction caused by oxidative stress gives rise to neurodegeneration in prion disease.
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PMID:Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent. 975 61

In the present study we evaluated the effects of NO synthase (NOS) induction on the regulation of cytochrome c oxidase (CO) and F0F1-ATPase subunit expression in astroglial and mixed cortical cell cultures. In mixed cortical cell cultures, 18 h of treatment with lipopolysaccharide (LPS, 0.1 microgram/mL) plus interferon-gamma (INF-gamma, 10 U/mL) caused an increase of mRNAs for CO-I, F0F1-ATPase 6 and also for iNOS at 20 DIV. The induction of both CO-I and F0F1-ATPase 6 was abolished by the NOS inhibitor N-monomethyl-L-arginine (NMMA) or by the enzymatic scavenger superoxide dismutase/catalase (SOD/CAT). In primary astroglial cell cultures, treatment for 18 h with increasing concentrations of LPS and INF gamma, produced an increase in the amount of mitochondrial encoded CO-I and -II subunits, with no significant modifications of nuclear encoded subunit IV. An increase was also observed at level of transcription for CO-I and -II, and F0F1-ATPase 6 mRNAs. These effects were abolished by addition of NMMA or SOD/CAT. mRNA induction of CO-I was higher in mixed cortical than in astroglial cell cultures while that of F0F1-ATPase 6 was similar in both cell types. These results suggest that the expression of mitochondrial encoded subunits (CO-I, CO-II and F0F1-ATPase 6) is up-regulated in response to oxygen and NO reactive species. The activity of cytochrome c oxidase decreased after LPS/INF gamma treatment in both astroglial and mixed cortical cultures. The activity of ATP synthase was unmodified, while ATP content drastically decreased after LPS/INF gamma treatment, in both astroglial and mixed cortical cultures. The enzymatic activities of catalase and Mn-SOD (mitochondrial) showed a significant increase after LPS/INF gamma treatment, which was abolished by NMMA.
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PMID:Effect of nitric oxide synthase induction on the expression of mitochondrial respiratory chain enzyme subunits in mixed cortical and astroglial cell cultures. 989 46

In 32D cl 3 hematopoietic progenitor cells, the overexpression of manganese superoxide dismutase (MnSOD, SOD2), the enzyme normally found in mitochondria, protects against the damaging effects of ionizing radiation. In the presence of a nitric oxide donor, which exacerbates the damage, inhibition of mitochondrial function can be demonstrated to be associated with respiratory complexes I (NADH dehydrogenase) and III (cytochrome c reductase), but not II (succinate dehydrogenase), IV (cytochrome c oxidase), or V (ATP synthase). The same pattern of inhibition is observed in the case of isolated bovine heart mitochondria exposed to ionizing radiation and the nitric oxide donor. The addition of authentic peroxynitrite (ONO2(-)) to isolated mitochondria also results in damage to complexes I and III (but not II, IV, and V), as shown by assays of electron-transfer activities and electron paramagnetic resonance (EPR) spectroscopic measurements, suggesting ONO2(-) to be responsible for most of the observed radiation damage in both the cultured cell lines and isolated mitochondria. It is argued that, in general, production of ONO2(-) is an important contributor to radiation damage in biological systems and the implications of these findings in relation to possible mechanisms of oxidant-linked apoptosis are briefly considered.
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PMID:Identification of respiratory complexes I and III as mitochondrial sites of damage following exposure to ionizing radiation and nitric oxide. 1129 62

Much interest has recently been shown in apoptosis-mediated roles in the pathophysiology of mitochondrial diseases, because mitochondrial defects are implicated in a wide variety of degenerative diseases. We investigated whether apoptotic events occurred in skeletal muscles of patients with mitochondrial diseases, including chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayer syndrome (KSS), and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). In a immunohistochemical study, stainings for 8-hydroxy-deoxyguanosine (8-OH-dG), 4-hydroxy-nonenal (4-HNE), Mn-SOD, Bcl-2, cytochrome c, DNase I and Bcl-x L showed a pronounced granular distribution in the cytochrome c oxidase (COX)-negative ragged-red fibers (RRFs). On the other hand, the signals for Bax, p53, Fas and caspase 3 were not obviously increased in RRFs. In situ labeling of DNA breaks demonstrated preferential signals not only in myonuclei but also in subsarcolemmal regions of RRFs, indicating that mitochondrial as well as myonuclear DNA is fragmented in RRFs. An immunoblotting study demonstrated that cytochrome c was increased in the cytosol of diseased muscles and that DNase I was increased in mitochondria, compared to that of normal muscles. No difference was observed between protein bands at 20 kDa corresponding to caspase 3 in diseased and normal muscles. These findings demonstrate that these mitochondrial diseases harbor unique apoptosis-related changes that differ from caspase 3-dependent apoptosis. It is thought that these changes are induced by superoxide overproduction and cytochrome c release resulting from an inherent mitochondrial defect and that the events are associated with DNase I activation.
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PMID:Apoptosis-related changes in skeletal muscles of patients with mitochondrial diseases. 1181 Jan 83

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.
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PMID:Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells. 1451 38

The involvement of mitochondrial glycerophosphate dehydrogenase (mGPDH) has previously been established in the production of ROS in prostate cancer cell lines (LNCaP, DU145, PC3 and CL1). The current study demonstrates that the mRNA level of mGPDH in prostate cancer cells is 3.3-8.9-fold higher compared to the normal prostate epithelial cell line, PNT1A. This is consistent with the enzymatic activity and protein level of mGPDH. However, cytochrome c oxidase (COX) activity is 2.9-3.2-fold down-regulated in androgen-independent prostate cancer cell lines. The level of antioxidant enzymes, catalase, MnSOD and CuZnSOD are up-regulated in prostate cancer cell lines. Furthermore, it was observed that the activity of mGPDH is significantly higher in liver tissues from all mice with cancer compared to liver tissues from control mice. These data suggest that the up-regulation of mGPDH, due to a highly glycolytic environment, contributes to the overall increase in ROS generation and may result in the progression of the cancer.
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PMID:Increased expression of mitochondrial glycerophosphate dehydrogenase and antioxidant enzymes in prostate cancer cell lines/cancer. 1788 33


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