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

Earlier histological studies have demonstrated that copper deficiency results in a selective and progressive atrophy of pancreatic acinar tissue. The present study examined both biochemical and morphological changes of the exocrine pancreas in nutritional copper deficiency. Groups of mature female rats were fed a purified diet either deficient (less than 0.5 micrograms/g) or sufficient (6.2 micrograms/g) in copper for 6 wk. Copper deficiency resulted in distinct ultrastructural changes in acinar cells, including marked variability in zymogen granule content, autophagic vacuoles and dilation of acinar lumen. Pancreatic weight and total DNA, RNA and protein content of the pancreas were similar in both groups of rats, whereas pancreatic amylase, trypsin and chymotrypsin activity was significantly lower in the copper-deficient group. In addition, secretagogue-induced release of these enzymes from dispersed acini isolated from copper-deficient rats was significantly reduced in comparison to enzyme secretion from normal controls. Pancreatic Cu-Zn and Mn superoxide dismutase activity was also found to be significantly lower in the copper-deficient rats than in normal controls. We conclude that nutritional copper deficiency in adult female rats reduces the responsiveness of the pancreas to secretagogues and may increase the susceptibility of the pancreas to oxidative damage.
 ...
PMID:Morphological and biochemical changes in the pancreas of the copper-deficient female rat. 247 34

A sublethal dose of D-penicillamine (DP) induced hyperlipoperoxidemia and hypocupremia in old rats. Treatment of cancer cells in vitro and in vivo with DP resulted in appreciable suppression of cell multiplication and a remarkable inhibition of tumor growth. Erythropoiesis did not seem to be affected by DP. The selective effect of DP seems to have resulted from the reduced superoxide dismutase activity and/or defective Mn superoxide dismutase.
 ...
PMID:Probable superoxide therapy of experimental cancer with D-penicillamine. 733 Aug 69

1. Control and copper-deficient rats were treated with: (i) indomethacin; (ii) indomethacin in the presence of cimetidine; and (iii) indomethacin in the presence of Cu(cimetidine)2. The levels of copper, zinc and manganese as well as the nature of superoxide dismutase activity in the liver were studied. 2. Copper deficiency caused a decrease of enzyme SOD activity, EDTA-insensitive (by 84%) and the appearance of nonenzyme SOD-like activity, EDTA-sensitive. The levels of copper and zinc decreased by 67% and 40% and the manganese level increased by 53%. 3. The above-mentioned treatments (i, ii, iii) of copper-deficient rats induced a progressive increase of enzyme SOD activity (by 19, 90 and 176%, respectively) without, however, changing nonenzyme SOD-like activity. It was only indomethacin treatment in the presence of Cu(cimetidine)2 that increased the copper level in control (by 82%) and copper-deficient (by 182%) rats. 4. The liver contained 4 CuZnSOD- and 1 MnSOD-isoenzymes, whose number and position on the gel were affected neither by copper deficiency nor by indomethacin treatment in the presence of Cu(cimetidine)2. Copper deficiency significantly increased the MnSOD-band and reduced the CuZnSOD-bands, particularly that with pI approximately 5.7. Indomethacin in the presence of Cu(cimetidine)2 changed neither the MnSOD-band nor the reduced CuZnSOD-band with pI approximately 5.7, but restored to normal all the other CuZnSOD-bands.
 ...
PMID:Do indomethacin and cimetidine or Cu(cimetadine)2 affect the nature of superoxide dismutase activity in the liver of copper-deficient rats? 795 24

Copper deficiency in rats resulted in a decrease of liver cytosolic and lysosomal CuZnSOD activity (by 71% and by 55%, respectively) and in an increase of mitochondrial MnSOD (by 185%). The content of copper and zinc decreased by 64% and 38%, respectively, and that of manganese increased by 47%. Cytosolic CuZnSOD activity, both in control and copper-deficient rats, increased (by 71.5 units/mg protein and by 83.0 units/mg protein, respectively) after indomethacin treatment. Rat liver contained four CuZnSOD (cytosolic and lysosomal) and one MnSOD isoenzyme. Neither copper deficiency nor indomethacin treatment changed the position and the number of bands. The CuZnSOD-band with pI approximately 5.7 was greatly decreased by copper deficiency and was not restored to normal after indomethacin treatment.
 ...
PMID:Liver superoxide dismutases after copper deficiency and/or indomethacin treatment of rats. 806 49

It is now widely accepted that abnormal prion proteins are the likely causative agent in bovine spongiform encephalopathy. Cellular prion proteins (PrP(c)) bind Cu, which appears to be required to maintain functional characteristics of the protein. The replacement of Cu on PrP(c) with Mn has resulted in loss of function and increased protease resistance. Twelve mature cows were used to determine the effects of Cu deficiency, alone and coupled with high dietary Mn, on brain Cu and Mn concentrations and on PrP(c) functional characteristics. Copper-adequate cows were randomly assigned to treatments: 1) control (adequate in Cu and Mn), 2) Cu-deficient (-Cu), and 3) Cu-deficient plus high dietary Mn (-Cu+Mn). Cows assigned to treatments -Cu and -Cu+Mn received no supplemental Cu and were supplemented with Mo to further induce Cu deficiency. After 360 d, Cu-deficient cows (-Cu and -Cu+Mn) tended to have lesser concentrations of Cu (P = 0.09) in the obex region of the brain stem. Brain Mn tended (P = 0.09) to be greater in -Cu+Mn cattle compared with -Cu cattle. Western blots revealed that PrP(c) relative optical densities, proteinase K degradability, elution profiles, molecular weights, and glycoform distributions were not different among treatments. The concentration of PrP(c), as determined by ELISA, was similar across treatment groups. Brain tissue (obex) Mn superoxide dismutase activity was greatest (P = 0.04) in cattle receiving -Cu+Mn, whereas immunopurified PrP(c) had similar superoxide dismutase-like activities among treatments. Immunopurified PrP(c) had similar Cu concentrations across treatments, whereas Mn was undetectable. We concluded that Cu deficiency, coupled with excessive Mn intake, in the bovine may decrease brain Cu and increase brain Mn. Copper deficiency, alone or coupled with high dietary Mn, did not cause detectable alterations in PrP(c) functional characteristics.
 ...
PMID:Exposure to low dietary copper or low copper coupled with high dietary manganese for one year does not alter brain prion protein characteristics in the mature cow. 1764 86

Heart mitochondria experience age-related declines in cytochrome c oxidase (CCO) activity and increases in the generation of reactive oxygen species (ROS) that may contribute to loss of cardiac function and the development of disease that occur with advancing age. In a manner similar to aging, copper deficiency also suppresses heart CCO activity and has cardiovascular consequences related to increased peroxidation. Food restriction is often used as a tool to study oxidative mechanisms of aging and the present study examines the potential of copper deficiency to model the role of mitochondria in cardiac aging by determining if the effect of food restriction on CCO activity and oxidative stress in heart mitochondria parallels its effect on cardiac mitochondria during aging. Overall, copper deficiency severely inhibited CCO activity and increased both Mn superoxide dismutase (MnSOD) and glutathione peroxidase (GPX) in isolated heart mitochondria. However, a 20% reduction in food intake by copper-deficient rats increased CCO activity by 65% and decreased MnSOD activity by 25% but had no effect in rats fed adequate copper. Copper deficiency also reduced the carbonyl content of 80-100 kDa mitochondrial proteins, but the reduction in carbonyl content was unaffected by food restriction. Food restriction did, however, completely prevent the enlargement of cardiac mitochondria in copper-deficient rats. Together, these findings indicate that copper deficiency induces mitochondrial antioxidant enzyme activity and hypertrophy in cardiac tissue in response to reduced CCO activity and that food restriction may counteract these changes by reducing oxidative stress. Because the action of food restriction on CCO activity and mitochondrially generated oxidative stress are similar in copper deficiency and aging, copper deficiency may serve as a short-term model for studying the potential roles of mitochondria in cardiac aging.
 ...
PMID:Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging. 2360 15