Effect of long-term cold exposure on antioxidant enzyme activities in a small mammal

Aerobic organisms continually face exposure to reactive oxygen species (ROS) and many have evolved sophisticated antioxidant systems to effectively remove them. Any increase in ROS production or weakening in this defense system may ultimately lead to oxidative stress and cellular damage. We investigated whether long-term cold exposure, which is known to lead to an elevation in metabolic rate, increased the activities of the ROS-scavenging enzymes, catalase (CAT), selenium-dependent glutathione peroxidase (GPx), and total superoxide dismutase (Total-SOD) in liver, cardiac muscle, kidney, skeletal muscle (vastus lateralis), and duodenum of short-tailed field voles (Microtus agrestis), born and maintained at either 8 ± 3°C or 22 ± 3°C. CAT, GPx, and Total-SOD activities were determined at age 61 ± 1.9 days. An increase in CAT activity in voles maintained at 8 ± 3°C was observed in skeletal muscle (71%) and kidney (20%), with both CAT and GPx activities significantly elevated (by 40 and 43%, respectively) in cardiac muscle, when compared to voles at 22 ± 3°C. Total-SOD activity and protein content did not differ significantly between groups in any tissue. We suggest that the compensatory increases in CAT (skeletal muscle, cardiac muscle, kidney) and GPx (cardiac muscle), but not Total-SOD activities, resulting from long-term cold exposure may reflect the elevated metabolic rate, and possibly also increased ROS production, at this time

Life-long vitamin C supplementation in combination with cold exposure does not affect oxidative damage or lifespan in mice, but decreases expression of antioxidant protection genes

Oxidative stress is suggested to be central to the ageing process, with endogenous antioxidant defence and repair mechanisms in place to minimize damage. Theoretically, supplementation with exogenous antioxidants might support the endogenous antioxidant system, thereby reducing oxidative damage, ageing-related functional decline and prolonging life- and health-span. Yet supplementation trials with antioxidants in animal models have had minimal success. Human epidemiological data are similarly unimpressive, leading some to question whether vitamin C, for example, might have pro-oxidant properties in vivo. We supplemented cold exposed (7 ± 2 °C) female C57BL/6 mice over their lifespan with vitamin C (ascorbyl-2-polyphosphate), widely advocated and self administered to reduce oxidative stress, retard ageing and increase healthy lifespan. No effect on mean or maximum lifespan following vitamin C treatment or any significant impact on body mass, or on parameters of energy metabolism was observed. Moreover, no differences in hepatocyte and lymphocyte DNA oxidative damage or hepatic lipid peroxidation was seen between supplemented and control mice. Using a DNA macroarray specific for oxidative stress-related genes, we found that after 18 months of supplementation, mice exhibited a significantly reduced expression of several genes in the liver linked to free-radical scavenging, including Mn-superoxide dismutase. We confirmed these effects by Northern blotting and found additional down-regulation of glutathione peroxidase (not present on macroarray) in the vitamin C treated group. We suggest that high dietary doses of vitamin C are ineffective at prolonging lifespan in mice because any positive benefits derived as an antioxidant are offset by compensatory reductions in endogenous protection mechanisms, leading to no net reduction in accumulated oxidative damage

The consequences of acute cold exposure on protein oxidation and proteasome activity in short-tailed field voles, microtus agrestis

During cold exposure, animals upregulate their metabolism and food intake, potentially exposing them to elevated reactive oxygen species (ROS) production and oxidative damage. We investigated whether acute cold (7 ± 3°C) exposure (1, 10, or 100 h duration) affected protein oxidation and proteasome activity, when compared to warm controls (22 ± 3°C), in a small mammal model, the short-tailed field vole Microtus agrestis. Protein carbonyls and the chymotrypsin-like proteasome activity were measured in plasma, heart, liver, kidney, small intestine (duodenum), skeletal muscle (gastrocnemius), and brown adipose tissue (BAT). Trypsin-like and peptidyl-glutamyl-like proteasome activities were determined in BAT, liver, and skeletal muscle. Resting metabolic rate increased significantly with duration of cold exposure. In skeletal muscle (SM) and liver, protein carbonyl levels also increased with duration of cold exposure, but this pattern was not repeated in BAT where protein carbonyls were not significantly elevated. Chymotrpsin-like proteasome activity did not differ significantly in any tissue. However, trypsin-like activity in SM and peptidyl-glutamyl-like activity in both skeletal muscle and liver, were reduced during the early phase of cold exposure (1–10 h), correlated with the increased carbonyl levels in these tissues. In contrast there was no reduction in proteasome activity in BAT during the early phase of cold exposure and peptidyl-glutamyl-like activity was significantly increased, correlated with the lack of accumulation of protein carbonyls in this tissue. The upregulation of proteasome activity in BAT may protect this tissue from accumulated oxidative damage to proteins. This protection may be a very important factor in sustaining uncoupled respiration, which underpins nonshivering thermogenesis at cold temperatures

Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition

Debate exists over the impact of caloric restriction (CR) on the level of energy expenditure. At the whole animal level, CR decreases metabolic rates but in parallel body mass also declines. The question arises whether the reduction in metabolism is greater, smaller or not different from the expectation based on body mass change alone. Answers to this question depend on how metabolic rate is normalized and it has recently been suggested that this issue can only be resolved through detailed morphological investigation. Added to this issue is the problem of how appropriate the resting energy expenditure is to characterize metabolic events relating to aging phenomena. We measured the daily energy demands of young and old rats under ad libitum (AD) food intake or 40% CR, using the doubly labeled water (DLW) method and made detailed morphological examination of individuals, including 21 different body components. Whole body energy demands of CR rats were lower than AD rats, but the extent of this difference was much less than expected from the degree of caloric restriction, consistent with other studies using the DLW method on CR animals. Using multiple regression and multivariate data reduction methods we built two empirical predictive models of the association between daily energy demands and body composition using the ad lib animals. We then predicted the expected energy expenditures of the CR animals based on their altered morphology and compared these predictions to the observed daily energy demands. Independent of how we constructed the prediction, young and old rats under CR expended 30 and 50% more energy, respectively, than the prediction from their altered body composition. This effect is consistent with recent intra-specific observations of positive associations between energy metabolism and lifespan and theoretical ideas about mechanisms underpinning the relationship between oxygen consumption and reactive oxygen species production in mitochondria

An investigation of the major and minor constituents of lithium niobate waveguides

5.00SIGLEAvailable from British Library Document Supply Centre- DSC:9091.9F(AERE-R--12026) / BLDSC - British Library Document Supply CentreGBUnited Kingdo