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R J Feuers

Publications and source records attributed to R J Feuers.

68 records · Page 4Linked to original sources
PubMed1989

Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in the male Fischer 344 rat.

It is well established that caloric restriction extends life span and significantly retards the rate of occurrence of most age-associated degenerative disease processes. A paucity of data exists relative to the mechanisms by which caloric restriction accomplishes these events. We have examined the effect of caloric restriction in rats on several hepatic enzymes of intermediary metabolism. The activities of glycolytic and supporting enzymes including lactate dehydrogenase, pyruvate kinase, sorbitol dehydrogenase, and alcohol dehydrogenase were all decreased in response to caloric restriction. Fructose 1-phosphate aldolase and creatine phosphokinase were not altered. Likewise, enzymes associated with lipid metabolism (malic enzyme and glycerokinase) were reduced (fatty acid synthetase was reduced, but not to a statistically significant degree). Activities of enzymes supporting gluconeogenesis (glutamate oxaloacetate transaminase, tyrosine aminotransferase, glutamate pyruvate transaminase, glutamate dehydrogenase, amino acid oxidase, malate dehydrogenase, and glucose 6-phosphatase) were either unchanged or increased significantly by caloric restriction. Glucagon levels were decreased. Comparisons between young ad libitum fed and older calorically restricted rats revealed similar but not identical metabolic activity. These results suggest that caloric restriction produces an effect on intermediary metabolism, favoring the role of glucagon and glucose synthesis; but limiting the role of insulin and glucose catabolism in the liver. The former observation provides for the efficient support of peripheral tissues and the latter a level of energy production necessary only for self maintenance. Limited lipid metabolism suggests decreased potential for fatty acid epoxide formation and free radical damage to cellular macromolecules. Additionally, caloric restriction may delay the progressive age associated changes in the activities of some of the enzymes investigated.

Age Factors↗
PubMed1987

Regulation of the circadian rhythm of hepatic pyruvate kinase in mice.

We have previously demonstrated circadian variation of pyruvate kinase (PK) activity. PK is a key enzyme of glycolysis, whose activity has been shown to be regulated at the level of enzyme concentration and catalytic activity. To investigate the mechanism of regulation and the components of the circadian rhythm of PK activity, Michaelis-Menten kinetic values were determined. C57BL/6J male mice that had been standardized for over 2 weeks to 12 hr light followed by 12 hr dark (lights on at 0600 hr CST), were killed at 3-hr intervals (six mice/circadian stage) over a 24-hr span. Vmax values, which are a measure of enzyme concentration, were found to be characterized by circadian variation (P = 0.01 by ANOVA, but P = 0.38 by cosinor analysis). The time of highest observed Vmax occurred at the early dark and continued through the entire dark and early light spans. An abrupt decrease in Vmax (-40%) was observed at the end of the light span. PK catalytic activity is regulated by covalent modification (phosphorylation/dephosphorylation) of the enzyme, and the phosphorylated, inactive form of the enzyme has a high Km for its major substrate (1.41 mM phosphoenol pyruvate; PEP). Km values were found to be characterized by a circadian rhythm (P less than 0.001 by cosinor analysis) whose acrophase (1117 hr) was at the beginning of the light cycle (high Km indicates low catalytic activity at subsaturating PEP concentrations). These results indicate that the circadian rhythm for PK activity is composed of at least two components. Enzyme concentration is high during the dark and early light phases but decreases at the end of the light phase. Concentration recovers rapidly within 3 hr after the lights are turned off. Catalytic activity is maximal at a time just after enzyme concentration becomes maximal in the dark phase. Maximal efficiency of the enzyme is thus achieved at the time when animals are eating and glycolysis is operating at high levels.

Animals↗
PubMed1987

Effect of age and torpor on the circadian rhythms of body temperature, activity, and body weight in the mouse (Peromyscus leucopus).

Age-related alterations in homeostatic mechanisms, as measured by changes in circadian rhythms, have been reported in the literature. The purpose of the present study was to determine if changes in the circadian rhythms of motor activity, body temperature, and body weight occur with age in the long-lived mouse, Peromyscus leucopus, and to determine if the incidence of torpor (hypothermia) was age-dependent. Young and old mice were entrained to an LD 12:12 cycle, and then physiological and behavioral performance was monitored by a data-acquisition system. The major differences between the 6-month and 60-72-month age groups were the following. Significant episodes of torpor occurred in a high percentage of old mice at 0600 hr on consecutive days, but young mice showed no evidence of torpor when food was provided ab libitum. Torpor in young mice was found to occur only during starvation conditions. Old animals phase in and out of torpor over an interval of several days; high-amplitude rhythms and good synchronization of activity and temperature occurred when torpor was expressed, and low-amplitude rhythms, poor synchronization between temperature and activity, and a phase shift of body-weight acrophase occurred on days when torpor was not expressed. Significant changes in acrophase and amplitude occurred between individual animals and days in the old group; no significant change in acrophase and amplitude was observed in the young group. Population-mean cosinor analysis revealed a significant age-related decrease in amplitude and mesor, but no significant change in acrophase was found.

Aging↗
PubMed1986

The effects of various lighting schedules upon the circadian rhythms of 23 liver or brain enzymes of C57BL/6J mice.

The activities of 23 brain or liver enzymes were studied in 5-6 week old C57BL/6JNctr male and female mice that had been fed ad libitum and standardized for 2 weeks to either (1) 12 hr of light (0600-1800) alternating with 12 hr of darkness (1800-0600) (LD 12:12), (2) staggered sequences of 12 hr of light and 12 hr of dark (SLD 12:12) or (3) continuous illumination (LL 12:12) for 2 weeks. Mice in the LD 12:12 and LL 12:12 experiments were killed at 4 hr intervals along a 24-hr span in order to sample at six different circadian stages. Lighting schedules for mice in the SLD 12:12 experiment were organized such that six different circadian stages were sampled when all mice were killed at one time of day. All 23 enzymes demonstrated a prominent circadian rhythm in at least one of the experiments. Moreover, about two-thirds of the enzymes in LD and SLD 12:12 had a statistically significant fit to a 24-hr cosine curve, while only one-third of the enzymes in LL 12:12 had significant fits to cosine curves. Peak activities of enzymes from mice in LD 12:12 were clustered at the time of transition from light to dark. This was also the trend for the activities of enzymes from mice in SLD 12:12, but resynchronization did not appear completed within the 2-week span. This, along with the observation that mesors (mean 24-hr activity) were reduced and amplitudes altered, indicated that the 2-week standardization period was not sufficient for some enzymes. Times of peak activities, mesors and amplitudes were affected for most enzymes from mice in the LL 12:12 environment. This suggests that individual mice became desynchronized from one another with respect to the original light-dark schedule and that rhythms were altered or lost because individual mice were free running with frequencies different from 24 hr.

Animals↗
PubMed1985

Ethyl methanesulfonate-induced mutations of major genes for quantitative phenotypes: mutant alleles for altered activity of brain or liver enzymes in C57BL/6J mice and their inheritance across several generations.

We recently identified and confirmed 8 induced mutations in the N2 and N3 progeny of ethyl methanesulfonate (EMS) treated C57BL/6J mice. Each of these mutations altered specific enzyme activities. These separate mutant sublines have been maintained through several generations as heterozygous mutant carriers. The percent decrease of the specific enzyme activity from normal in each subline was calculated for each generation. Additionally, the percentage of breeders within each mutant subline producing abnormal progeny and the fraction of such breeders' total progeny possessing abnormal activity were determined. The aberrant activity values observed in progeny of a confirmed mutant carrier were all lower than normal. 4 of the mutant sublines had decreases in enzyme activities which were constant across the generations analyzed. 3 of the mutant sublines had decreases in activities which were consistent over early generations but changed significantly in later generations. Another subline with decreased enzyme activity was lost. For 7 of the sublines, the number of progeny having altered activity and the number of breeders producing mutant progeny approximated that expected for single gene inheritance. In the remaining subline, a change in the decrease in enzyme activity probably accounts for the deviation from expected inheritance. Although the phenotypes for these quantitative traits are considered to be quasi-continuous, the data indicate that the mutations are probably of major genes.

Alleles↗
PubMed1985

The effect of age on the circadian rhythms of 23 liver or brain enzymes from C57BL/6J mice.

Mice were standardized to 12 h of light exposure alternating with 12 h of darkness and were fed ad libitum. The mice in the first group were 8 weeks old and in the other 104-116 weeks old. Subgroups of 7 animals from each age group were killed at 6 circadian stages. Enzyme activities of 23 enzymes from liver or brain were measured by an analysis of variance for each age group. All but 1 enzyme from young mice, and all but 9 from older mice showed significant changes over time (p less than 0.01). The data from the 22 enzymes from young mice and the 14 enzymes from old mice were fit to the cosinor regression model to further characterize the rhythm. 15 enzymes from the young and 8 from the aged mice showed a significant regression to a 24-hour cosine curve (p less than 0.01); of the 8, 7 were the same enzymes in both groups. Amplitude changes, where they could be compared from the cosinor data (7 enzymes), were not statistically different. When total variance was compared, 12 enzymes showed unequal variance. Of these, old mice had the larger variance in 9 enzymes. Another difference between the young and the old was changes in mean enzyme activities. 12 enzymes from aged mice had decreased mesors, 2 had increased mesors, and 9 were unchanged. In general, our data suggest that some enzyme activity rhythms were lost, others were altered and a few were not affected by aging. In the case of many enzymes, older mice have a diminished ability to synchronize to the light signals.

Animals↗
PubMed1984

Insulin and glucagon's reciprocal mediation of a dual regulation mechanism for pyruvate kinase.

The addition of glucagon to hepatocytes in primary culture produced a rapid and sustained increase in the Km (1.27 mM phosphoenol pyruvate) of pyruvate kinase. The low Km (0.4 mM) form of the enzyme was seen when cells were retreated with insulin, demonstrating a short-term regulation mechanism. Injections of insulin, glucagon or glucagon followed by insulin demonstrated that a similar mechanism occurs in vivo. Results from longer times after injection indicated that another mechanism occurs when altered activity was the result of changes in V max and not Km. Thus, a dual mechanism for regulation of pyruvate kinase occurs. A rapid responding system functions by modification of the enzyme, while a long-term system functions by altering the rate of synthesis, thus changing the amount of enzyme present.

Animals↗
PubMed1984

Circadian dependent effect of epidermal growth factor, insulin and glucagon on hepatic pyruvate kinase and malic enzyme of mice.

The influence of epidermal growth factor (EGF), 0.75 micrograms g1; insulin, 1.5 micrograms g-1; glucagon, 1.25 micrograms g-1 and their combinations on the activities of hepatic pyruvate kinase (PK) and malic enzymes (ME) was monitored. Male CD2F1 mice were treated toward the end of the light or dark periods, 9 or 23 hours after lights on (9 or 23 HALO), and subgroups of six mice were killed at 4, 8 or 12 hr post-treatment. PK and ME activities from control mice were well characterized by cosine curves. The PK activity was maximal when ME activity was minimal at the transition from light to dark (9 HALO plus 4 hr) and PK was at a minimum when ME was highest (23 HALO plus 4 hr). Both enzymes were influenced by at least one peptide hormone, and the effects were strongly circadian-stage dependent. The only effect attributed to EGF was an increase of PK activity (23%) 12 hr after injection at 23 HALO. PK activity was increased by insulin (23%) at 23 HALO (4 hr after injection), but not at 9 HALO, and decreased (17%) by glucagon 12 hr after injection at 9 HALO. Several reductions in PK activity in response to various combinations of peptides were observed, and appeared to be caused by glucagon but influenced by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Pleiotropic and other genetic effects influencing the activities of brain and liver enzymes in congenic lines of C57BL/6J mice with defined electrophoretic variant markers.

A single genetic factor may affect the realization of several enzymes. To investigate the extent of pattern pleiotropy in the mouse, the activities of 28 enzymes in livers and brains from an inbred stock of C57BL/6JNctr and five F1 stocks heterozygous for known electrophoretic variants were measured. Five congenic backcross stocks of C57BL/6J, each homozygous for one or more electrophoretic markers, were mated with C57BL/6JNctr to construct the heterozygous variant F1 stocks. One of the five F1 stocks had no enzyme activities significantly different from those of C57BL/6JNctr, while two had one enzyme, one had four enzymes, and another had six enzymes with activities that were significantly different from those of C57BL/6JNctr. The latter two F1 stocks with multiple activity differences were those having the largest proportion of their genome of donor origin. Two of the F1 stocks were different from each other for one enzyme, and two were different for another enzyme. These differences and the relationship of these enzyme activities to the variant genes suggest that several genetic factors may affect an enzyme's realization.

Animals↗
PubMed1982

Development of a new biochemical mutation test in mice based upon measurements of enzyme activities. I. Theoretical concepts and basic procedure.

A test procedure is described for detecting germ cell mutations which alter activity of enzymes in in vivo mammalian tissues. The objective is to identify those individuals, among a population of F1 animals from treated parents, that are heterozygous for a mutation at an unspecified locus which results in an altered activity of one or more of the enzymes monitored. Animals are evaluated through three analysis screens with emphasis on identification of mutant individuals. In the first screen, activity values of a battery of enzymes are compared to their respective normal ranges to identify those which are aberrant. The mean activities and coefficients of variation useful in defining the normal ranges for 19 enzymes in C57BL/6J Nctr mice are presented along with a set of theoretical normal animal misclassification probabilities for each of these enzymes. The second screen is a Michaelis-Menten kinetic analysis of aberrant enzymes, the goal of which is to correct misclassifications of normal animals made in the first screen. A third screen of aberrant enzyme activities in a subsequent generation is used to demonstrate inheritance and confirm the mutation. The advantages and the limitations, as well as possible variations of the basic procedure are discussed.

Animals↗
PubMed1981

Circadian organization of thirteen liver and six brain enzymes of the mouse.

The activities of 13 liver and 6 brain enzymes were studied in 7-12 week old CD2F1 male mice that had been fed ad libitum and standardized either to 12 hours of light (0600-1800) alternating with 12 hours of darkness (1800-0600) (LD12:12); or to a reversed light-dark cycle (darkness 0600-1800; light 1800-0600) (DL12:12). Three separate studies were performed on two different days; in each experiment, subgroups of 14 animals were sacrificed at 3-hour intervals. Livers were assayed for: isocitrate dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, glutathione reductase, glyoxylate reductase, L-alanine aminotransferase, glutamate oxalacetate transaminase, pyruvate decarboxylase, fructose-1-phosphate aldolase, fructose diphosphate aldolase, fructose 1,6-diphosphatase, and fatty acid synthetase. Brains were assayed for phosphoglucose isomerase, adenosine triphosphatase, creatine phosphokinase, pyruvate kinase, adenylate kinase, and malate dehydrogenase. All 19 enzymes demonstrated a prominent circadian rhythm in at least one experiment. Moreover, each rhythmic variable showed a statistically significant fit to a 24-hour cosine (sine) curve by the method of least squares. In general, peak activities of the liver enzymes analyzed were associated with the beginning of the dark cycle and initiation of the animal's activity, while the group of brain enzymes had peak activities which occurred at the beginning of the animals' rest span and were near the beginning of the light cycle. The phasing of each of the rhythms could be reversed within a two-week span after reversing the environmental light-dark cycle 180 degrees.

Animals↗