Manganese Superoxide Dismutase In Heart Research Articles

Effect of dietary manganese on antioxidant status and expression levels of heat-shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

Oxidative Stress Causes Heart Failure with Impaired Mitochondrial Respiration

Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O(2)(*)(-)), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of a superoxide dismutase mimetic significantly ameliorated the symptoms. These results implied that O(2)(*)(-) generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventions.

MnSOD in mouse heart: acute responses to ischemic preconditioning and ischemia-reperfusion injury

Manganese superoxide dismutase (MnSOD) is one of the main antioxidant enzymes that protects the heart against ischemia-reperfusion (I/R) injury. Ischemic preconditioning (IPC) is a short period of ischemia-reperfusion that reduces subsequent prolonged I/R injury. Although MnSOD localizes in mitochondria, the immediate subcellular distribution of MnSOD in heart after IPC and I/R has not been studied. In a Langendorff mouse heart model, IPC significantly improved cardiac function and reduced the infarction size induced by I/R. Immunoblotting and double immunostaining in fresh preparations revealed that I/R resulted in an increase in cytosolic MnSOD content accompanied by the release of cytochrome c. In contrast, IPC increased mitochondrial MnSOD and reduced cytosolic MnSOD and cytochrome c release induced by I/R. We found that compared with freshly prepared fractions, the freeze-thaw approach results in mitochondrial integrity disruption and release of large amounts of MnSOD into the cytosol along with mitochondrial markers even in the absence of I/R. In contrast, fresh preparations exhibit early MnSOD release into the cytosol after I/R that is prevented by IPC and cyclosporin A administration.

Antioxidant and oxidative status in tissues of manganese superoxide dismutase transgenic mice

Manganese superoxide dismutase (Mn-SOD) plays an important role in attenuating free radical–induced oxidative damage. The purpose of this research was to determine if increased expression of Mn-SOD gene alters intracellular redox status. Twelve week old male B6C3 mice, engineered to express human Mn-SOD in multiple organs, and their nontransgenic littermates were assessed for oxidative stress and antioxidant status in heart, brain, lung, skeletal muscle, liver, and kidney. Relative to their nontransgenic littermates, transgenic mice had significantly ( p < .01) higher activity of Mn-SOD in heart, skeletal muscle, lung, and brain. Copper, zinc (Cu,Zn)-SOD activity was significantly higher in kidney, whereas catalase activity was lower in brain and liver. The activities of selenium (Se)-GSH peroxidase and non-Se-GSH peroxidase, and levels of vitamin E, ascorbic acid and GSH were not significantly different in any tissues measured between Mn-SOD transgenic mice and their nontransgenic controls. The levels of malondialdehyde were significantly lower in the muscle and heart of Mn-SOD mice, and conjugated dienes and protein carbonyls were not altered in any tissues measured. The results obtained showed that expression of human SOD gene did not systematical alter antioxidant systems or adversely affect the redox state of the transgenic mice. The results also suggest that expression of human SOD gene confers protection against peroxidative damage to membrane lipids.

Effects of sex and age on manganese metabolism in rats

The objective of this study was to examine the effects of growth or differences in sex on Mn metabolism of rats fed diets deficient or adequate in Mn. Weanling male and female rats were fed diets containing less than 1 mg Mn/kg (MnD) or 47 mg Mn/kg diet (MnS). Four weeks before they were killed, at ages of 7, 11, and 15 weeks, each rat was fed a test meal containing 54Mn. Absorption and excretion of 54Mn were determined by measuring whole body retention of 54Mn for four weeks using a small animal whole body counter. Animals were killed after a 20 hour fast. Tissue Mn and activity of liver arginase (LA) and heart manganese-superoxide dismutase (Mn-SOD) were measured. Rats fed MnS absorbed less and excreted more Mn than those fed MnD. Dietary deficiency of Mn markedly decreased (3 to 4 times) femur or liver. Mn concentration, plasma cholesterol and LA and SOD activity were decreased by Mn deficiency, but cholesterol and LA were not affected by sex or age of the rats. Male rats accumulated and utilized more Mn than did female rats by decreasing the rate of Mn excretion. Older rats absorbed less Mn and excreted Mn more slowly than younger rats. Changes in femur Mn with age did not vary with sex or amount of dietary Mn. Female rats were as vulnerable as males to the effects of Mn deficiency.

Influence of manganese intake on body, wool and testicular growth of young rams and on the concentration of manganese and the activity of manganese enzymes in tissues

Four groups of 10-month-old Merino rams of similar liveweights were fed identical diets, except that the manganese contents were either 13, 19, 30 or 45 pg/g of dry matter. The basal diet (13 8g Mn/g) was fed to all rams for 14 days, then the treatment diets were fed for a further 84 days. All rams were slaughtered at the end of the experiment and tissues were collected. The intake of manganese had no affect on liveweight gain, dry matter intake, apparent digestibility of the diet or clean wool production. Although the size of testicles at slaughter was not related to manganese intake, testicular gain as a ratio to liveweight gain was higher in the rams fed 19 and 30 pg Mn/g, but not 45 8g Mn/g, than those fed 13 8g Mn/g. Also in rams fed the basal diet, the large rumen bacteria (12.90 to 16.24 pm in diameter) made up less of the bacterial biomass than in other groups. The treatments did not affect the total number of rumen bacteria or the size structure of bacteria population in the rumen. Rams fed the least amount of manganese had low concentrations of manganese in heart and lung and a lower activity of manganese superoxide dismutase in heart than rams fed 45 8g Mn/g. The concentration of manganese in these tissues, and the activity of manganese superoxide dismutase in the heart increased linearly as the concentration of manganese in the diet increased. An intake of 13 8g Mn/g of dry matter therefore caused some biochemical changes in rams, but was adequate for growth and wool production under the conditions of this experiment.