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Biomedical subjects

R J Feuers

Publications and source records attributed to R J Feuers.

At least 19 recordsLinked to original sources
PubMed2003

Assessment and significance of 24-h energy intake patterns among young and aged non-affluent southern US women.

Energy intake patterns that may impact health status among non-affluent southern U.S. women from small urban communities have not been evaluated extensively. Usual intake estimates are confounded by factors such as validity of intake methods and socioeconomic status. Typical 24-h energy intakes were reported by Caucasian (CA, n=149) and African-American (AA, n=110) women; at 43% of this sub-population, AA women are appropriately and proportionately represented. Daily energy intake was examined for these non-pregnant females, 24 to 93 y of age, to define typical energy, carbohydrate, protein, and fat intake. Study groups were: 24-29 y, 30-39 y, 40-49 y, 50-59 y, 60-69 y, 70-79 y, and 80-93 y. Statistical comparisons of nutrient variables by age were made by least squares means between groups. Body mass index (BMI) calculations accounted for differences in height and relative body mass. Both races reported similar energy intakes and significant (P<0.05) decreases with age were noted. Energy intakes were 15-40% below recommended levels, similar to reported values; senior lunch programs ameliorated declines among some women >60 y. More daily calories (52-62%) were provided by carbohydrates, followed by fat (26-35%) and protein (14-17%) findings in close agreement with health recommendations. Time-of-day intake patterns suggest women >59 y consume larger noon meals. BMI for AA women was greater (P<0.05) than that of CA women between 30-59 y. At 24-29 y, AA women had lowest BMI values; BMI decreases occurred in CA women after 80 y. These factors may impact the health of non-affluent southern AA and CA women, particularly the elderly who may require guidance for diet planning and intake intervention programs.

Adult↗
PubMed2003

Assessment of antioxidant nutrient intake of a population of southern US African-American and Caucasian women of various ages when compared to dietary reference intakes.

Antioxidant nutrient intervention strategies to ameliorate negative health factors are of notable research interest. Central to the thesis that antioxidant nutrients improve biological defense systems and provide health benefits is an accurate indication of daily antioxidant nutrient intake. Little information is available concerning these nutrient intakes among non-affluent women of the southern U.S. This study examines the 24-h intake of vitamins: A, E, C, -carotene, a-tocopherol, riboflavin, and minerals: zinc, selenium, copper, manganese, iron, and molybdenum among 259 Caucasian (CA) and African-American (AA) women from small urban communities. Women were non-pregnant females, 19-93 y of age. Statistical comparisons of nutrient intake were made by least squares means within age groups. Intakes were compared to various Dietary Reference Intakes including Recommended Daily Allowance (RDA) and Estimated Average Requirement (EAR) values as established by the U.S. National Research Council. Numerous dietary deficiencies in important antioxidant nutrients associated with metabolic antioxidant systems were identified. Few race-related differences were detected. Intake of vitamin A was generally within recommended levels while vitamin E intake was below the EAR. The vitamin precursors, -carotene and a-tocopherol, were significantly (P<0.05) below customary intakes at all ages. More than 60% of this population reported dietary copper, zinc, and selenium intakes below recommended levels. A lack of race differences for most nutrient intakes suggests similar socioeconomic or endogeneous regional factors. All women in this population reported dietary intakes of antioxidant vitamins and minerals below recommended values, conditions that could contribute to subsequent health risks unless nutrient-dense food choices and antioxidant supplementation are considered in their overall nutritional support.

Adult↗
PubMed2001

Activity profile of glutathione-dependent enzymes and respiratory chain complexes in rats supplemented with antioxidants and treated with carcinogens.

Appropriate dietary interventions may reduce the potentially damaging effects of free radicals generated during metabolism and various physiological conditions. We have investigated the effects of dietary vitamins C, E, beta-carotene, or selenium (Se) on the activity of endogenous antioxidant enzymes and respiratory chain complexes in rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA), a mammary carcinogen and bleomycin (BLM), an antineoplastic drug. These agents are known to generate DNA-reactive species during their metabolism, which may enhance oxidative stress in cells. Female Fischer 344 rats aged 4 months were given antioxidant supplements singly or as a mixture 2 weeks prior to mutagen treatments; antioxidant supplementation continued for an additional 4 weeks. In rats treated with mutagens, the antioxidant intake lowered the activity of Se-dependent glutathione peroxidase (Se-GPx) in liver cytosolic and mitochondrial fractions, compared to activity in rats treated with mutagens alone. However, the vitamins, but not Se supplement, persistently increased Se-GPx activity in untreated control animals. Treatment of animals with mutagen raised K(m) value of Se-GPx and this correlated with an increase in V(max). However, Se intake, either singly or mixture, significantly reduced K(m) value in mutagen-treated and untreated rats in both fractions. Se intake increased glutathione S-transferases (GST) activity (P < 0.05) in both liver fractions of mutagen-treated and untreated animals. Similar response was seen in Se-independent GPx. Since GST-alpha possesses Se-independent GPx activity, the enhanced effect observed in GST activity may be due, in part, to increased activity in Se-independent GPx. Also, selenium or the antioxidant vitamin supplementation increased the activity of all four respiratory chain complexes in untreated rats. Although BLM treatment significantly increased the activity of electron transport complexes III and IV, selenium or the vitamin supplements modulated the responses. These results indicate that the intake of dietary vitamins or Se enhances antioxidant capacity in chemically exposed animals compared to animals receiving antioxidants alone. Furthermore, in addition to being an enhancer of the catalytic function of glutathione peroxidase, selenium may directly play a role as an antioxidant.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: implications for chronic studies.

A study was undertaken to determine the effects of incremental levels of dietary restriction (DR) in rats. Survival, growth, reproductive, and dietary intake (DI) variables were monitored in a chronic study in which male Sprague Dawley (SD) rats (NCTR colony) were fed their ration ad libitum (AL), or DR. The main objectives were to determine if low levels of DR could be used to increase the survival rate of SD rats in the chronic bioassay, and to identify the survival characteristics of a long-lived SD rat strain (NCTR colony). The average life span of AL rats was 115 months. At 104 weeks on study (110 weeks of age), the survival rate for the AL and 10%, 25%, and 40% DR groups was 63.4, 87.5, 87.5, and 97.5%, respectively. The largest increase in survival (24.1%) occurred between AL and 10% DR, indicating that very low levels of DR have a significant effect on survival. Whole-body, liver, prostate, and epididymis weights and body length were decreased by DR, whereas brain weight, testicular weight, and skull length were not altered by DR. Rats from the NCTR colony were found to be ideal for chronic studies because they are much longer-lived than other SD stocks. Although the 104-week survival rate for these SD, non-obese AL rats exceeds the FDA's "Redbook" survival guideline (> 50%) for chronic bioassays, the use of DR is advocated because it reduces individual variability in body weight.

Aging↗
PubMed2001

Influence of body fat distribution on oxygen uptake and pulmonary performance in morbidly obese females during exercise.

OBJECTIVE: The aim of this study was to determine the effects of fat distribution on aerobic and ventilatory response to exercise testing in morbidly obese (MO) females. METHODOLOGY: The study population consisted of 164 MO females, 55% (n = 90) with upper body or abdominal adiposity (UBD), as defined by waist-hip circumference ratio (WHR) > or = 0.80, and 45% (n = 74) with lower body fat distribution (LBD) (WHR < 0.80). An incremental exercise testing on cycle ergometer was performed to determine the effect of exercise on oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), tidal volume (VT), respiratory rate (fb) and heart rate (HR). RESULTS: Upper body adiposity individuals had significantly higher VO2 and VCO2 than LBD subjects (P < 0.05) from 0 watt (W) of pedalling up to their anaerobic threshold (AT) and maximal exercise. VE was significantly higher in UBD subjects compared with LBD subjects, from 20 W during exercise up to AT and peak work levels (P < 0.05). Upper body adiposity group also had a significantly higher fb than the LBD group at rest, after each workload and at AT and peak exercise work rates (P < 0.05). VT was lower in UBD subjects at free pedalling and up to AT and peak workload with significant difference at 60 and 80 W (P < 0.05). The anaerobic threshold, expressed as work rate, was significantly lower in the UBD subjects (P < 0.05) and peak workload achieved did not differ significantly between the two groups. CONCLUSIONS: Upper body adiposity subjects had higher oxygen requirement, more rapid and shallow breathing, higher ventilatory demand, but lower anaerobic threshold than the LBD individuals during progressive exercise. It suggests that the cardiopulmonary endurance to exercise in MO patients with upper body fat distribution is lower than in those with lower body fat distribution.

Adipose Tissue↗
PubMed2001

Caloric restriction mimetics: metabolic interventions.

Caloric restriction (CR) retards diseases and aging in laboratory rodents and is now being tested in nonhuman primates. One way to apply these findings to human health is to identify and test agents that may mimic critical actions of CR. Panel 2 focused on two outcomes of CR, reduction of oxidative stress and improved glucoregulation, for which candidate metabolic mimics exist. It was recommended that studies on oxidative stress should emphasize mitochondrial function and to test the efficacy of nitrone and other antioxidants in mimicking CR's effects. Studies should also focus on the long-term effects of compounds known to lower circulating glucose and insulin concentrations or to increase insulin sensitivity. Also, four other developing areas were identified: intermediary metabolism, response to infection, stress responses, and source of dietary fat. These areas are important because either they hold promise for the discovery of new mimetics or they need to be explored prior to initiation of CR trials in humans. Other recommendations were that transgenic approaches and adult-onset CR should be emphasized in future studies.

Animals↗
PubMed2000

Effects of bleomycin on liver antioxidant enzymes and the electron transport system from ad libitum-fed and dietary-restricted female and male Fischer 344 rats.

Dietary restriction (DR) is the only known intervention that delays aging and age-related diseases. Mechanisms proposed to explain this DR effect include a decline in free radical production and an increase in free radical detoxification. In the present study the effect of bleomycin (BLM) as a reactive oxygen species-generating antitumor drug has been evaluated on antioxidant enzymes and the electron transport system in different cellular fractions of liver in female and male Fischer 344 rats. Animals were fed ad libitum (AL) or 60% of the AL intake (DR) and were given a single intraperitoneal injection of 2.5, 5, or 10 mg BLM/kg body wt. After four weeks, BLM significantly increased glutathione peroxidase and lactate dehydrogenase activities in liver cytosol of female AL rats and increased activity even more in male rats. Similar changes were also noted for glutathione reductase and glucose 6-phosphate dehydrogenase activities in BLM-treated AL rats. In liver mitochondria, glutathione peroxidase was increased in female and male AL rats but was increased more in female rats. Drug treatment had no significant effect on these enzyme activities in cytosolic or mitochondrial fractions of DR animals. Profound effects of BLM were noted in activities of complexes I, III, and IV of the electron transport system in AL and DR female and male rats; however, complex II demonstrated no significant diet or treatment effect. Induced antioxidant enzyme activities in BLM-treated AL rats may be a response to excessive free radical generation due to BLM metabolism in AL animals that is mitigated by DR. Furthermore, dysfunction of the electron transport system might suggest its role in a secondary generation of free radicals during BLM metabolism contributing to its toxicity.

Animals↗
PubMed1999

Attenuation of bleomycin-induced Hprt mutant frequency in female and male rats by calorie restriction.

Calorie restriction modulates spontaneous and chemically induced tumors and increases maximal life span in experimental animals; however, the mechanism by which calorie restriction exerts its ameliorating effects is not fully elucidated, although reduced levels of reactive oxygen species (ROS) by calorie restriction has generated much interest. In the present study, we have determined whether or not calorie restriction would affect the mutagenic response in rats treated with bleomycin (BLM) a radiomimetic drug that is associated with DNA damage by a free radical mechanism. Fourteen weeks after weaning, the rats were divided into two groups; ad libitum (AL)-fed and 40% calorie restriction. Both AL and calorie-restricted animals were injected with 2.5, 5.0 and 10.0 mg BLM/kg, or with phosphate-buffered saline (PBS), and they were killed 4 weeks post drug treatment. Lymphocytes from the spleens were seeded in 96-well microtiter plates to determine mutant frequency in the hypoxantine guanine phosphoribosyl transferase (Hprt) gene. The mutant frequency in the BLM-treated rats was higher in AL males (P=0.001), and AL females (P=0.0174) than in their calorie-restricted counterparts. The difference in mutagenic response relative to AL males and AL females appeared unrelated to a low percent cloning efficiency seen in the males, since the mean absolute number of Hprt mutant clones was higher in the AL males compared to the females. A reduction in animal weight by calorie restriction was significant in both sexes (P<0.001), but the dose effect appeared non-significant. The results indicate that calorie intake of 60% reduced the mutagenic response of BLM, a compound known to induce oxidative DNA damage, and suggest a possible decrease in ROS as a function of calorie restriction.

Animals↗
PubMed1999

The relationship of p53 and stress proteins in response to bleomycin and retinoic acid in the p53 heterozygous mouse.

A single, i.p. dose of bleomycin was administered simultaneously with [35S]methionine to 4-month-old p53 wild type (+/+) and p53 heterozygous (+/-) C57BL/6 mice. Following a period of 3.5 h from dosing, the bone marrow nuclei were examined by two-dimensional PAGE and fluorography for induction of stress proteins (sps). Eight sps ranging from 22000 to 100000 Mr were synthesized in p53+/- and p53+/+ mice following elicitation by bleomycin. No quantitative or qualitative differences were observed in sp expression in these two groups of animals. In a second experiment, three doses of retinoic acid were given i.p. to p53+/- and p53+/+ mice over a 36 h period. The p53 isoforms in bone marrow nuclei from these mice were analyzed by PAGE for incorporation of [35S]methionine following retinoic acid injections. Quantitative and qualitative alterations in p53 isotypes were substantially increased in p53+/+ as compared with p53+/- mice. The increased complexity in the synthesis patterns in both groups of dosed mice consisted of additional isoforms possessing more acidic isoelectric values. In an in vitro binding assay, individual p53 isoforms demonstrated varying degrees of association with sps 25a, 70i, 72c and 90 which was consistently greater in p53+/+ mice. Both the synthesis and binding of isoforms were greater in G1 than in S+G2 phase, in both groups of animals, reflecting a cell cycle regulated mechanism for these events. Collectively, these data implied that the synthesis and the binding characteristics of p53 isoforms with sps were enhanced in the p53+/+ mice relative to the p53+/- mouse; however, sp labeling was not affected by p53 genotype.

Animals↗
PubMed1998

The effects of dietary restriction on mitochondrial dysfunction in aging.

Age-associated alterations in the mitochondrial electron transport system (ETS) may lead to free radical generation and contribute to aging. The complexes of the ETS were screened spectrophotometrically in gastrocnemius of young (10 month) as well as older (20 and 26 month) B6C3F1 female mice fed an ad libitum (AL) diet or a restricted (DR) in total calories diet (40% less food than AL mice). The activities of complexes I, III, and IV decreased significantly by 62%, 54%, and 74%, respectively, in old AL mice (AL20) compared to young AL mice (AL10). Complexes I, III, and IV from DR10 mice had activities that were significantly lower than those seen in AL10 mice (suggesting a lower total respiratory rate or improved efficiency). By contrast, complex II activity did not decrease with age (actually increased, but not significantly) in AL20 mice. Complex II was decreased across age in DR mice. K(m) for ubiquinol-2 of complex III was significantly increased in AL10 animals (0.33 mM vs. 0.26 mM in DR10 mice) and was further increased with aging (0.44 mM in AL20 vs. 0.17 mM in DR20 mice). This suggests obstruction of binding, inhibition of electron flow in aging, which could yield premature product release as a free radical. Total complex IV by Vmax was highest in AL10 mice, but the proportion of complex as high-affinity sites was lower (69%) than in either DR10 (80%) or DR20 (80%). The percentage of high-affinity sites decreased to only 45% in AL20 mice, and Vmax was reduced by 75 percent. In AL26 mice high-affinity sites decreased to 33 percent. At physiologic concentration of reduced cytochrome c, significant dysfunction of complex IV in AL20 or AL26 mice would be expected with obstruction of overall electron transport. The age-associated loss of activity and function of complexes I, III, and IV may contribute to increased free radical production. Lack of sufficient DNA repair in mitochondria and juxtaposition to the ETS adds to susceptibility and accumulation of mtDNA and other mitochondrial macromolecular damage. DR seems to retard this deterioration of mitochondrial respiratory function by preserving enzymatic activities and function.

Aging↗
PubMed1998

Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils.

BACKGROUND: As assessed by flow cytometry, the increase in hydrogen peroxide in individual neutrophils from old volunteers was significantly greater than in neutrophils from young volunteers. To explain the discrepancy in previous reports that showed reduced superoxide generation with age and our finding, we measured the kinetics of antioxidative enzymes. METHODS: Neutrophils were obtained from young (ages 21-34) and old (ages over 65) volunteers. The increase in hydrogen peroxide following stimulation with formyl peptide in individual neutrophils was assessed by flow cytometry by using dihydrorhodamine 123. The enzyme kinetics was determined from the best fit curve using Michaelis-Menten equations. RESULTS: Aging was associated with a significant reduction in the Vmax for glutathione peroxidase. The decreased activity was not due to selenium deficiency as the serum and neutrophil concentrations were identical with age. Following activation, a significant increase in the Km was noted in neutrophils from young but not from old volunteers. CONCLUSIONS: These results account for the increased intracellular accumulation of hydrogen peroxide as a function of age in stimulated neutrophils. These results provide evidence in humans of an age-related impairment in antioxidative defense mechanisms that support the free radical theory of aging.

Adult↗
PubMed1997

Age and temperature related changes in behavioral and physiological performance in the Peromyscus leucopus mouse.

Age-related and ambient temperature-related changes in motor activity, body temperature, body weight (b.w.), and food consumption were studied in the long-lived Peromyscus leucopus mouse at environmental temperatures of 29 and 21 degrees C. Major changes in physiological performance were observed between the young (6 months) and old (60-72 month) age groups. The number of daily activity episodes, and total activity output was significantly lower in old mice. Maximum, average and minimum daily body temperature was lower in the old mice and a significant ambient temperature-by-age interaction was found. Maximum, minimum, and average daily b.w. was higher in old mice. Motor activity was evenly distributed over the active (night) phase in young mice but in old mice activity was significantly greater in the late night partition of the active cycle than in the early night partition. Both groups were significantly more active at night than during the day. Most of the food consumption in both groups occurred at night, but young mice consumed significantly more during the late night partition than the early night partition, and the consumption rates for old mice were not significantly different between early and late night partitions. The percentage of activity episodes involved with food consumption in both groups was significantly higher during the night partition, but the percentage during the early night partition was significantly higher in old mice than in young mice. Significant episodes of circadian torpor occurred in a high percentage of old mice at 06:00, on consecutive days, at both environmental temperatures, but young mice expressed no evidence of torpor.

Aging↗
PubMed1997

P53 synthesis and phosphorylation in the aging diet-restricted rat following retinoic acid administration.

Multiple doses of retinoic acid (RA) were administered intraperitoneally to three groups of male Fischer 344 rats over a 36 h period. The p53 isoforms from bone marrow nuclei in these three groups of rats were analyzed over time by two-dimensional polyacrylamide gel electrophoresis (PAGE) and fluorography for the incorporation of [35S]methionine (p53-synthesis) and [32P]phosphate (p53-phosphorylation). Two groups of rats, young (3.5 months) ad libitum (Y/AL) and old (28 months) ad libitum (O/AL), had free access to Purina rat chow; a third group of old (28 months) diet-restricted rats (O/DR) were maintained on a restricted caloric intake (60% of the AL diet) from 3 months of age. After 36 h of RA dosing, the PAGE patterns of p53 synthesis and phosphorylation in Y/AL and O/DR rats were very similar. In both groups, an increase in complexity was observed with labeling of additional isotypes possessing more acidic isoelectric values. In contrast, the O/AL animals showed a pattern of p53 isoform synthesis and phosphorylation that was considerably less complex and lacked the pronounced shift to more acidic forms following RA dosing. The p53 isoforms of O/AL rats as recognized by wild type (wt) Pab 246 antibody, were also much less dramatic in their increase to more acidic forms. Two-dimensional phospho-tryptic maps of Y/AL and O/DR rats were also very similar, both exhibiting two additional minor 32P-labeled fragments after RA dosing. The maps of O/AL rats did not show the two additional fragments following RA administration. After RA dosing, cyclin protein inhibitors (p16, p21, p27) revealed robust labeling with their respective antibodies in Y/AL and O/DR rats as analyzed by Western blotting. The O/AL animals showed marginally detectable antibody recognition of the cyclin inhibitors after RA dosing. Taken together, these data suggest that the biosynthesis and phosphorylation of p53 isoforms and the expression of cyclin dependent kinase inhibitor proteins is not significantly different between Y/AL and O/DR rats. Further, these results confirm and extend our previous observations that chronic diet-restriction attenuates the age related decline in the metabolic activity of nuclear protein products.

Aging↗
PubMed1997

Modulation of antioxidant enzymes in bleomycin-treated rats by vitamin C and beta-carotene.

Bleomycin (BLM), an antineoplastic drug, is known to induce DNA strand breaks and is also mutagenic in mammalian cells; however, its mechanism of action is not well understood. It has been proposed that BLM cytotoxicity is mediated through the generation of reactive oxygen species. We have determined the effects of BLM on endogenous hepatic antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase, and glucose-6-phosphate dehydrogenase in rats exposed to BLM in conjunction with dietary vitamins, vitamin C and beta-carotene (BC). Male Fischer 344 rats of two different age groups were treated with BLM in the presence or absence of antioxidant vitamins. In control animals, an age-associated decrease in GPx activity was noted (p < 0.05). The decrease in GPx activity observed in BLM-treated old animals given vitamin C was significant (p < 0.05) compared with BLM-treated young animals fed vitamin C. BC moderately induced GPx and glutathione reductase activities in old BLM-treated animals; however, the increase in GPx was statistically significant (p < 0.05) only compared with old controls. A similar increase was noted in the activities of all the enzymes examined in young animals. Our results indicate that BLM exposure was accompanied by alterations in the activities of endogenous antioxidant enzymes, with a profound increase in activities occurring in old animals. In addition, the observed enzyme activities were modulated by antioxidant vitamin administration. The observation that both vitamins displayed differential effects on the enzyme activities also suggests that vitamin C and BC exert their effects by separate mechanisms.

Age Factors↗
PubMed1996

Influences of age and dietary restriction on gastrocnemius electron transport system activities in mice.

Alterations in the mitochondrial electron transport system (ETS) may contribute to aging. Dietary restriction (DR) provides a model to investigate retarded aging. ETS activities were measured in gastrocnemius from 10- and 20-month-old B6C3F1 female mice fed either ad libitum (AL) or DR diets (40% < AL). Older (26 month old) AL mice were studied for complex IV. Activities of complexes I, III, and IV decreased 54-74% from 10 to 20 months of age in AL mice. At 10 months, activities of complexes I, III, and IV were 33-64% lower in DR compared to AL mice. The Km for ubiquinol-2 of complex III increased 29% by 20 months of age in AL mice while no change occurred in DR mice. The Vmax of complex IV declined by 90% from 10 to 26 months of age in AL mice and this change was opposed by DR. Complex IV contains high- and low-affinity binding sites. The Km for high-affinity sites was not influenced by age or diet through 20 months; however, the Km was approximately twofold higher at 26 months in AL mice. The percentage of total binding sites which were of high affinity fell from 68% at 10 months in AL mice to 46% at 20 months and was even lower (33%) at 26 months. This value was 80% for DR mice at 10 and 20 months. These alterations with aging in mitochondrial ETS capacities may contribute to decreases in skeletal muscle function.

Aging↗
PubMed1996

MPP(+)-induced neurotoxicity in mouse is age-dependent: evidenced by the selective inhibition of complexes of electron transport.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been demonstrated to cause selective neurotoxicity by inhibiting complex I in mitochondria, through its toxic metabolite 1-methyl-4-phenylpyridine (MPP+) which is formed during the bioactivation of MPTP by monoamine oxidase B. In this report, we have evaluated the effect of MPP+ on the 4 mitochondrial respiratory chain complexes by incubating brain mitochondria of mice at 3 different age groups with MPP+ (200 microM) and monitoring enzyme activities of complexes I, II, III, and IV at 5, 10, 15, 30, 60, and 120 min. Complexes I, III, and IV showed significant inhibition within 15 min in all the age groups studied, followed by some recovery in enzyme activities upon further incubation for complexes I and IV. However, complex II was not affected by MPP+ at any age. Our data suggest that inhibition of complexes I, III, and IV by MPP+ efficiently restrict the transport of electrons down the respiratory chain which ultimately leads to decreased ATP production. This could further aggravate oxidative stress as ATP is required for the synthesis of glutathione (GSH), one of the important scavengers of free radicals. In this study, inhibition was more severe in mitochondrial preparations from older rather than younger mice. Additionally, young animals showed faster recovery following inhibition than old animals for complex I. Impaired respiratory chain function in older animals compared to younger ones supports the hypothesis of accumulation of age-related mitochondrial DNA mutations which partly encode for subunits of complexes I, III, and IV. From this study, it seems that inhibition of complexes I, III, and IV may be the underlying cause of neurotoxicity due to MPP+ which could be intensified by age-associated dysfunction of electron transport.

1-Methyl-4-phenylpyridinium↗
PubMed1996

Characterization of rat lymphocyte primary culture for the development of an in-vitro mutagenesis assay: effect of interleukin-2 and 2-mercaptoethanol on the activities of intermediary metabolism enzymes and cell proliferation.

Efficient energy utilization is essential for cell growth; in an attempt to improve the growth conditions of the rat T-lymphocyte culture model for potential use in studying the mutagenic activity of carcinogens in vitro, we have investigated the effects of phytohemagglutinin (PHA), interleukin-2 (IL-2) and 2-mercaptoethanol (2-ME) on the activities of intermediary metabolism enzymes and cell proliferation. Isolated lymphocytes were cultured in the presence and absence of PHA, IL-2, or 2-ME. The intermediary metabolism enzymes investigated were glutamate dehydrogenase, glutamate-pyruvate transaminase, malate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, pyruvate kinase, and fatty acid synthetase (FAS). Measurable activity of all enzymes investigated, except for FAS, was detected in PHA-stimulated cells cultured with IL-2 or 2-ME. The unstimulated lymphocytes had significantly lower enzyme activity than stimulated cells. The combination of all three agents showed increased enzyme activity. This increase in activity brought about by the combination of the three agents was not reproduced by either agent acting alone. In general, the increase in enzyme activity correlated with cell proliferation as measured by [3H]thymidine uptake in PHA-stimulated cultures containing IL-2 and/or 2-ME. The results suggest that the addition of exogenous IL-2 and 2-ME enhances metabolic function and may be beneficial in in vitro culture of rat lymphocytes.

Amino Acids↗