Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When the cellular production of ROS exceeds the cell's antioxidant capacity, cellular ...macromolecules such as lipids, proteins and DNA can be damaged. Because of this, 'oxidative stress' is thought to contribute to aging and pathogenesis of a variety of human diseases. However, in the last 10-15 years, a considerable body of evidence has accumulated that ROS serve as subcellular messengers, and play a role in gene regulation and signal transduction pathways, which may be involved in defensive mechanisms against oxidative stress. This review focuses on oxidative stress caused by the inactivation of glutathione peroxidase (GPx), a major peroxide scavenging enzyme. GPx is inactivated by a variety of physiological substances, including nitric oxide and carbonyl compounds in vitro and in cell culture. Decreased GPx activity has also been reported in tissues where oxidative stress occurs in several pathological animal models. The accumulation of increased levels of peroxide resulting from inactivation of GPx may act as a second messenger and regulate expression of anti-apoptotic genes and the GPx itself to protect against cell damage. These findings suggest that GPx undergoes inactivation under various conditions such as nitroxidative stress and glycoxidative stress, and that these changes are a common feature of various types of oxidative stress which may be associated with the modification of redox regulation and cellular function.
The aim of this study was to evaluate whether high-intensity endurance training would alleviate exercise-induced oxidative stress. Nine untrained male subjects (aged 19-21 years) participated in a ...12-week training programme, and performed an acute period of exhausting exercise on a cycle ergometer before and after training. The training programme consisted of running at 80% maximal exercise heart rate for 60 min.day-1, 5 days.week-1 for 12 weeks. Blood samples were collected at rest and immediately after exhausting exercise for measurements of indices of oxidative stress, and antioxidant enzyme activities superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) in the erythrocytes. Maximal oxygen uptake (VO2max) increased significantly (P < 0.001) after training, indicating an improvement in aerobic capacity. A period of exhausting exercise caused an increase (P < 0.01) in the ability to produce neutrophil superoxide anion (O2.-) both before and after endurance training, but the magnitude of the increase was smaller after training (P < 0.05). There was a significant increase in lipid peroxidation in the erythrocyte membrane, but not in oxidative protein, after exhausting exercise, however training attenuated this effect. At rest, SOD and GPX activities were increased after training. However, there was no evidence that exhausting exercise enhanced the levels of any antioxidant enzyme activity. The CAT activity was unchanged either by training or by exhausting exercise. These results indicate that high-intensity endurance training can elevate antioxidant enzyme activities in erythrocytes, and decrease neutrophil O2.- production in response to exhausting exercise. Furthermore, this up-regulation in antioxidant defences was accompanied by a reduction in exercise-induced lipid peroxidation in erythrocyte membrane.
The effects of endurance training on the enzyme activity, protein content, and mRNA abundance of Mn and CuZn superoxide dismutase (SOD) were studied in various phenotypes of rat skeletal muscle. ...Female Sprague-Dawley rats were randomly divided into trained (T, n = 8) and untrained (U, n = 8) groups. Training, consisting of treadmill running at 27 m/min and 12% grade for 2 h/day, 5 days/wk for 10 wk, significantly increased citrate synthase activity (P < 0. 01) in the type I (soleus), type IIa (deep vastus lateralis, DVL), and mixed type II (plantaris) muscles but not in type IIb (superficial vastus lateralis, SVL) muscle. Mitochondrial (Mn) SOD activity was elevated by 80% (P < 0.05) with training in DVL. SVL and plantaris muscle in T rats showed 54 and 42% higher pooled immunoreactive Mn SOD protein content, respectively, than those in U rats. However, no change in Mn SOD mRNA level was found in any of the muscles. CuZn SOD activity, protein content, and mRNA level in general were not affected by training, except for a 160% increase in pooled CuZn SOD protein in SVL. Training also significantly increased glutathione peroxidase and catalase activities (P < 0.05), but only in DVL muscle. These data indicate that training adaptations of Mn SOD and other antioxidant enzymes occur primarily in type IIa fibers, probably as a result of enhanced free radical generation and modest antioxidant capacity. Differential training responses of mRNA, enzyme protein, and activity suggest that separate cellular signals may control pre- and posttranslational regulation of SOD.
1. The present study was undertaken to investigate the effects of hypobaric hypoxia, equivalent to an altitude of 5500 m,
on antioxidant enzymes in rats. 2. Malondialdehyde levels in serum, heart, ...lung, liver and kidney of hypobaric-hypoxic rats
were all significantly higher than in control rats by day 21 of exposure (P < 0.05), indicating increased oxidative stress.
3. Superoxide dismutase (SOD) catalyses the conversion of the superoxide anion to H2O2 and O2. The concentration of immunoreactive
Mn-SOD in the serum of hypobaric-hypoxic rats was raised significantly from day 5 onwards, whereas in liver and lung, it had
decreased significantly by day 21 (P < 0.05). 4. Glutathione peroxidase (GSH-Px) catalyses H2O2 and certain lipid peroxides.
By day 21, GSH-Px activity had increased significantly in the heart and lungs, but decreased significantly in the liver (P
< 0.05). 5. Catalase catalyses H2O2. Catalase activity in the liver and kidney of hypobaric-hypoxic rats was significantly
decreased on day 1 (P < 0.05) though levels then recovered. 6. Mn-SOD mRNA in the liver of hypobaric-hypoxic rats was induced
during the experiment, the effect being exceptionally marked, especially during the first 3 days of exposure to hypobaric
hypoxia. 7. These results suggest that the liver may be more vulnerable than the other organs tested to oxidative stress under
hypobaric hypoxia.
Site-specific and random fragmentation of human Cu,Zn-superoxide dismutase (Cu,Zn-SOD) was observed following the glycation
reaction (the early stage of the Maillard reaction). The fragmentation ...proceeded in two steps. In the first step, Cu,Zn-SOD
was cleaved at a peptide bond between Pro62 and His63, as judged by amino acid analysis and sequencing of fragment peptides,
yielding a large (15 kDa) and a small (5 kDa) fragment. In the second step, random fragmentation occurred. The ESR spectrum
of the glycated Cu,Zn-SOD suggested that reactive oxygen species was implicated in the both steps of fragmentation. The same
fragmentations were seen upon exposure of the enzyme to an H2O2 bolus. Catalase completely blocked both steps of the fragmentation
process, whereas EDTA blocked only the second step. Incubation with glucose resulted in a time-dependent release of Cu2+ from
the Cu,Zn-SOD molecule. The released Cu2+ then likely participated in a Fenton's type of reaction to produce hydroxyl radical,
which may cause the nonspecific fragmentation. Evidence that EDTA abolished only the second step of fragmentation induced
by an H2O2 bolus supports this mechanism. This is the first report that a site-specific fragmentation of a protein is caused
by reactive oxygen species formed by the Maillard reaction.
The influence of ageing on the expression of two superoxide dismutase (SOD) isozymes was examined in three different skeletal muscle fiber types of young (Y, 8 mo) and old (O, 25 mo) rats. Total SOD ...activity was increased with age in the gastrocnemius (Gas, type II
mix) and superficial vastus lateralis (SVL, type IIb) but unchanged in the soleus (Sol, type I). The increased SOD activity in SVL was due to increased cytosolic SOD (CuZn SOD), whereas both mitochondrial (Mn SOD) and CuZn SOD activities were increased in Gas. In Sol, Mn SOD activity was significantly increased in aged rats. Mn SOD mRNA level was significantly decreased with age in all three muscles examined, while Mn SOD protein content was not altered. Ageing did not affect CuZn SOD mRNA abundance in any of the muscles, but significantly increased CuZn SOD protein content in aged Gas and Sol. Binding of two redox-sensitive transcription factors, nuclear factor-κB (NFκB) and activator protein-1 (AP-1) was significantly decreased with age in all three muscle types. These results indicate that increased SOD activity in aged skeletal muscle is not associated with higher levels of gene transcription. Increases in Mn SOD activity seen in aged Gas and Sol are the result of post-translational modification of the enzyme, whereas increases in CuZn SOD activity during ageing may be due to both translational and post-translational control.
A total of 191 fishermen and their family (32–82 years) living in some mercury-polluted areas along the Shiranui Sea volunteered for the present study. They made a living by fishery and had formerly ...eaten the methyl mercury-contaminated fish and shellfish caught there. The questionnaire on subjective symptoms, fish eating habits, and past living history was conducted on the subjects. In addition, they were clinically examined in detail by several neurologists and scalp hair was collected. With six exceptions, all the 185 subjects showed a normal total mercury level in hair (<10 ppm). The ratio of methyl mercury to total mercury was 79–94% on the average for each group examined, suggesting indirect contamination (perhaps through the food chain). Despite their low mercury level in scalp hair, however, the subjects showed various neurological symptoms, particularly, sensory disturbance (such as the glove and stocking type), at a very high rate. Thus, it seems fair to state that, in addition to officially recognized Minamata disease patients, there still exist many people with atypical, slight Minamata disease on the coast of the Shiranui Sea. The current hair mercury level is not necessarily useful as a criterion for diagnosing chronic Minamata disease because of the long lapse of time.
Our previous study indicated that erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes glycation and inactivation in vivo (1) and in vitro (2). The aim of the present study was to assess ...glycated Cu,Zn-SOD in patients with insulin-dependent diabetes mellitus. Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay. The percentage of the glycated form in 25 insulin-dependent diabetic children was 40.2 +/- 8.2%; this was significantly higher than that in the normal controls (P less than 0.01). The specific activity of the glycated form in the diabetic children was 163,000 +/- 33,000 IU/mg Cu,Zn-SOD protein, significantly lower than that in controls (P less than 0.01). These data indicate that glycated and less active Cu,Zn-SOD is increased in erythrocytes of patients with insulin-dependent diabetes mellitus.
The stress relaxation in an inclusion bearing material at high temperatures under an external load has been examined. Independently from the analysis by Mori et al. (
Acta mater., 1997,
45, 429), it ...has been ascertained that the material reveals steady-state creep even with only matrix plastic flow (multiaxial power-law creep) operating, through both variational principles analysis and finite element method (FEM). The characteristic of nonuniform stress distribution, which brings about steady-state creep, has been discussed. The dependence of the steady-state creep rate on inclusion aspect ratio and volume fraction has been also obtained through FEM analysis.
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