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B Lonnerdal

Publications and source records attributed to B Lonnerdal.

At least 19 recordsLinked to original sources
PubMed2006

Iron at the center of ferritin, metal/oxygen homeostasis and novel dietary strategies.

Bioiron - central to respiration, photosynthesis and DNA synthesis and complicated by radical chemistry with oxygen - depends on ferritin, the super family of protein nanocages (maxi-ferritins in humans, animals, plant, and bacteria, and mini-ferritins, also called DPS proteins, in bacteria) for iron and oxygen control. Regulation of ferritin synthesis, best studied in animals, uses DNA transcription and mRNA translation check points. Ferritin is a member of both the "oxidant stress response" gene family that includes thioredoxin reductase and quinine reductase, and a member of the iron responsive gene family that includes ferroportin and mt-aconitase ferritin DNA regulation responds preferentially to oxidant response inducers and ferritin mRNA to iron inducers: heme confers regulator synergy. Ferritin proteins manage iron and oxygen, with ferroxidase sites and iron + oxygen substrates to form mineral of both Fe and O atoms; maxi-ferritins contribute more to cellular iron metabolism and mini-ferritins to stress responses. Iron recovery from ferritin is controlled by gated protein pores, possibly contributing to iron absorption from ferritin, a significant dietary iron source. Ferritin gene regulation is a model for integrating DNA/mRNA controls, while ferritin protein function is central to molecular nutrition cellular metabolism at the crossroads of iron and oxygen in biology.

Animals↗
PubMed2001

Frataxin expression rescues mitochondrial dysfunctions in FRDA cells.

Friedreich's ataxia (FRDA) is the result of mutations in the nuclear-encoded frataxin gene, which is expressed in mitochondria. Several lines of evidence have suggested that frataxin is involved in mitochondrial iron homeostasis. We have transfected the frataxin gene into lymphoblasts of FRDA compound heterozygotes (FRDA-CH) with deficient frataxin expression to produce FRDA-CH-t cells in which message and protein are rescued to near-physiological levels. FRDA-CH cells were more sensitive to oxidative stress by challenge with free iron, hydrogen peroxide and the combination, consistent with a Fenton chemical mechanism of pathophysiology, and this sensitivity was rescued to control levels in FRDA-CH-t cells. Iron challenge caused increased mitochondrial iron levels in FRDA-CH cells, and a decreased mitochondrial membrane potential (MMP), both of which were rescued in FRDA-CH-t cells. The rescue of the low MMP, and high mitochondrial iron concentration by frataxin overexpression suggests that these cellular phenotypes are relevant to the central pathophysiological process in FRDA which is aggravated by exposure to free iron. However, even at physiological iron concentrations, FRDA-CH cells had decreased MMP as well as lower activities of aconitase and ICDH (two enzymes supporting MMP), and twice the level of filtrable mitochondrial iron (but no increase in total mitochondrial iron), and the observed phenotypes were either fully or partially rescued in FRDA-CH-t cells. Free iron is known to be toxic. The observation that frataxin deficiency (either directly or indirectly) causes an increase in filtrable mitochondrial iron provides a new hypothesis for the mechanism of cell death in this disease, and could be a target for therapy.

Aconitate Hydratase↗
PubMed1999

The Friedreich's ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis.

Expansions of an intronic GAA repeat reduce the expression of frataxin and cause Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease. Frataxin is a mitochondrial protein, and disruption of a frataxin homolog in yeast results in increased sensitivity to oxidant stress, increased mitochondrial iron and respiration deficiency. These previous data support the hypothesis that FRDA is a disease of mitochondrial oxidative stress, a hypothesis we have tested in cultured cells from FRDA patients. FRDA fibroblasts were hypersensitive to iron stress and significantly more sensitive to hydrogen peroxide than controls. The iron chelator deferoxamine rescued FRDA fibroblasts more than controls from oxidant-induced death, consistent with a role for iron in the differential kinetics of death; however, mean mitochondrial iron content in FRDA fibroblasts was increased by only 40%. Treatment of cells with the intracellular Ca2+chelator BAPTA-AM rescued both FRDA fibroblasts and controls from oxidant-induced death. Treatment with apoptosis inhibitors rescued FRDA but not control fibroblasts from oxidant stress, and staurosporine-induced caspase 3 activity was higher in FRDA fibroblasts, consistent with the possibility that an apoptotic step upstream of caspase 3 is activated in FRDA fibroblasts. These results demonstrate that FRDA fibroblasts are sensitive to oxidant stress, and may be a useful model in which to elucidate the FRDA mechanism and therapeutic strategies.

Apoptosis↗
PubMed1998

Uptake of 125I-labelled alpha2-macroglobulin and albumin by human placental syncytiotrophoblast in vitro.

We have investigated the binding and internalization of alpha2-macroglobulin and serum albumin by human placental syncytiotrophoblast cells in vitro. The time course (obtained at 4 degrees C) of alpha2-macroglobulin binding indicated that an equilibrium was reached after 4 h. The binding of 125I-labelled alpha2-macroglobulin to syncytiotrophoblast cells was competitively reduced in the presence of excess unlabelled alpha2-macroglobulin. When the concentration-dependence of binding was examined over a wide concentration range, non-linear regression analysis yielded a Kd of 6.4 nM. In the case of albumin, binding was weak and ligand dissociated from the cell surface during aqueous washing making it impractical to analyze the binding reaction. In other experiments, syncytiotrophoblast cells were incubated with 125I-labelled alpha2-macroglobulin at 37 degrees C. Under these conditions, trypsin-resistant cell-associated radioactivity increased with time consistent with ligand internalization. 125I-labelled-ligand was internalized with a t1/2 of about 5 min. After a lag period some radioactivity was released back into the incubation medium. When measured at times up to 210 min, this was found to consist of mostly TCA-precipitable material that had been lost from the cell surface. However, when the incubation was extended to 24 h, almost 15% of the initial cell-associated radioactivity was released to the extracellular medium as TCA-soluble material, consistent with a slow rate of ligand degradation. The specific binding of 65Zn-labelled alpha2M was similar to that of the 125I-labelled ligand and trypsin-resistance measurements provided evidence of alpha2M-mediated 65Zn uptake. These results support a role for syncytiotrophoblast in the metabolism of alpha2-macroglobulin during pregnancy and are also consistent with a role for alpha2-macroglobulin in the maternal-fetal transport of zinc.

Cells, Cultured↗
PubMed1995

Extracellular superoxide dismutase activity is affected by dietary zinc intake in nonhuman primate and rodent models.

Assessment of zinc nutriture is often compromised by the lack of reliable biomarkers. In the present study the effect of dietary zinc deprivation on plasma extracellular superoxide dismutase (EC SOD) activity was investigated in rat and rhesus macaque models. This enzyme, which contains both zinc and copper, is distinct from cytosolic copper-zinc SOD. Young, growing rats fed zinc-deficient diets (1.5 nmol Zn/g diet) were characterized by low plasma zinc concentrations and plasma EC SOD activities (16% and 56% of controls, respectively). Adolescent rhesus macaques fed diets that contained a marginal amount of zinc (30.6nmol Zn/g diet) also had low plasma zinc concentrations and low EC SOD activities compared with controls fed diets containing 765 nmol Zn/g diet (75% and 40%, respectively). Enzyme activity was not affected after in vitro addition of zinc to plasma samples from control, restrict-fed, and zinc-deficient rats. Taken together, these data support the concept that plasma EC SOD activity can be a biomarker for zinc status.

Animals↗
PubMed1994

Modulation of behavioral performance of prepubertal monkeys by moderate dietary zinc deprivation.

Young rhesus monkeys (Macaca mulatta, n = 14) 25-30 mo of age were fed a zinc-deficient (ZD) diet (2 micrograms Zn/g diet) (moderate zinc deprivation) over 15 week. The ZD diet period was compared with a zinc-adequate (ZA) diet period (50 micrograms Zn/g diet) of the same duration, which either preceded or followed it (crossover design). Plasma zinc was lower at the end of the ZD than after the ZA period. There were no overt signs of zinc deficiency or effects on growth rate. Spontaneous motor activity was lower and performance of a visual-attention task and short-term-memory task were poorer during the ZD period than during the ZA period. Behavioral effects were detected as changes from individual baseline values, and often represented a failure to improve. The results suggests that dietary zinc deprivation can modulate behavior in prepubertal monkeys without affecting growth.

Animals↗
PubMed1994

Lactoferrin-receptor interaction. Effect of surface exposed histidine residues.

Specific receptors for lactoferrin (Lf) have been identified in the small intestine brush-border membrane and on lymphocytes. Little is known about the mechanism of Lf interaction with its receptor protein. Because of the pH dependence of this interaction, the possible involvement of surface exposed histidine residues was explored. His residues on purified human milk Lf were progressively modified by carboxyethylation with diethyl pyrocarbonate; the reaction was monitored by UV absorbance and by affinity chromatography on immobilized Cu(II) ions. Human infant brush-border membrane vesicles (BBMVs) were prepared by differential centrifugation and precipitation methods. Human peripheral lymphocytes were prepared by Ficoll centrifugation and stimulated by mitogen (PHA) exposure in culture. A competitive receptor binding assay was performed with 59Fe- and/or 125I-labelled native Lf and His-modified Lf. Binding assays with labelled native Lf were conducted in the presence of a 10-200 fold molar excess of DEPC-Lf, the DEPC-Lf was not competitive. A 100-fold molar excess of native Lf completely blocked the interaction of labelled Lf with the receptor. Similar results were obtained for receptor proteins on BBMVs and lymphocytes. Thus, Lf receptors on these two different cell types appear to require His residues for Lf binding.

Adult↗
PubMed1993

Energy and protein intakes of breast-fed and formula-fed infants during the first year of life and their association with growth velocity: the DARLING Study.

Intake and growth were compared between matched cohorts of infants either breast-fed (BF) or formula-fed (FF) until > or = 12 mo of age. Total energy intake at 3, 6, 9, and 12 mo averaged 0.36, 0.34, 0.35, and 0.38 MJ.kg-1.d-1 (85.9, 80.1, 83.6, and 89.8 kcal.kg-1.d-1) among BF infants vs 0.41, 0.40, 0.39, and 0.41 MJ.kg-1.d-1 (98.7, 94.7, 93.6, and 98.0 kcal.kg-1.d-1) among FF infants, respectively. Protein intake was 66-70% higher in the FF than in the BF group during the first 6 mo. Differences in energy and protein intakes were significant at 3, 6, and 9 mo. Gains in weight and lean body mass were lower in BF than in FF infants from 3 to 9 mo. BF infants gained more weight and lean body mass per gram protein intake but not per megajoule intake. Although growth differences between groups were related to differences in intake, there is no evidence of any functional advantage to the more rapid growth of FF infants.

Body Height↗
PubMed1993

Intake and growth of breast-fed and formula-fed infants in relation to the timing of introduction of complementary foods: the DARLING study. Davis Area Research on Lactation, Infant Nutrition and Growth.

We examined if the timing of introduction of solid foods was related to growth, intake, morbidity, activity or motor development among infants either breast fed or formula fed until > or = 12 months of age. Breast-fed infants given solids before 6 months of age (earlysol) consumed less breast milk at 6 and 9 months of age than those given solids > or = 6 months (latesol); thus total energy intake did not differ between groups. Z scores for weight, length and weight-for-length at 1-18 months did not differ between groups. Latesol infants gained less weight from 6 to 9 months but not during any other interval. Neither activity level nor morbidity differed between groups, but several developmental milestones occurred earlier in the earlysol versus the latesol group, probably due to reverse causation. Among formula-fed infants, timing of introduction of solid foods was not related to intake, growth, activity or morbidity. We conclude that solid foods given before 6 months of age generally replace the milk source among breast-fed but not formula-fed infants.

Adult↗
PubMed1993

Alterations in intestinal uptake and compartmentalization of zinc in response to short-term dexamethasone therapy or excess dietary zinc in piglets.

Premature infants receive high dietary zinc and often glucocorticoids as a treatment for chronic lung disease. A piglet model was developed to investigate intestinal zinc transport and distribution of tissue zinc in response to treatment with short-term (5 d) glucocorticoid therapy or a high zinc diet. Piglets (13-15 d old; n = 21) were randomly allocated to: 1) dexamethasone (DEX) therapy (1.5 mg/kg intramuscularly twice a day), 2) high zinc diet (15.3 mmol/kg), or 3) control group (0.3 mmol dietary zinc/kg and saline intramuscularly twice a day). Pig weight, formula intake, urine volume, and blood glucose were monitored. At necropsy, tissue samples were obtained to measure zinc in plasma and zinc and metallothionein in liver and small intestinal mucosa. Velocity of zinc uptake by intestinal brush border membrane vesicles was measured using 65Zn tracer. Maximum uptake rate and Km for zinc uptake by brush border membrane vesicles were significantly greater (p < 0.05) in DEX compared with control and high zinc groups. DEX-treated piglets had a significantly lower (p < 0.05) zinc efflux rate across brush border membrane vesicles compared with that of the control. The high zinc group had a higher liver (p < 0.05) and mucosal (p < 0.05) zinc content and higher liver metallothionein concentration (p < 0.001) compared with the control and DEX groups. Weight gain over 5 d was not different among groups. Daily blood glucose was higher (p < 0.05) in DEX versus control and high zinc groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of the severity of maternal zinc deficiency on pregnancy outcome and infant zinc status in rhesus monkeys.

To investigate the effects of the severity of maternal zinc deficiency on early development, rhesus monkeys were fed diets that were either moderately zinc-deficient (MZD) (2 micrograms Zn/g) or marginal in zinc (M) (4 micrograms Zn/g) throughout pregnancy and lactation. Dams in the MZD group developed overt signs of zinc deficiency. Compared with control dams fed diets adequate in zinc (C) (50 or 100 micrograms Zn/g), both M and MZD dams showed low mitogen response. Pregnancy outcome was similar in all groups, and infants were considered healthy at delivery. From birth until d 30, infants were closely monitored for signs of zinc deficiency. On d 30, infants were killed and tissues were analyzed for several parameters reported to be affected by zinc status. MZD infants tended to have lower plasma zinc concentrations than C infants, although the difference was only significant at d 14. M infants tended to have lower plasma zinc concentrations than C infants. Mitogen response was lower in MZD and M infants than in C infants. However, mitogen responses were similar in MZD and M infants. Liver zinc concentrations were similar among the three groups of infants; however, zinc and metallothionein concentrations in (10,000 x g) liver supernatant fractions were lower in the MZD and M groups than in the C group. 65Zn absorption/retention was higher in MZD and M mothers and infants than in C mothers and infants; there were no marked differences between MZD and M mothers or infants. In contrast to whole-body absorption, 65Zn uptake/retention by isolated hepatocytes was similar among the three infant groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Ultrasound evaluation of fetuses of zinc-deprived monkeys (Macaca mulatta).

Fetal body movements were studied in three groups of gravid rhesus macaques fed different amounts of dietary zinc (100 micrograms Zn/g diet, control, n = 12; 4 micrograms Zn/g diet, marginal deprivation, n = 7; 2 micrograms Zn/g diet, moderate deprivation, n = 11). Sonographic examinations were conducted during the third trimester in awake chair-restrained dams. Movement categories, derived from the human biophysical profile, were motor activity (trunk and limb movements), startle, and breathing movements. Moderately deprived fetuses were more active than controls on gestational day (GD) 115; maternal plasma zinc concentrations were significantly correlated with fetal activity at this time. In addition moderately deprived fetuses exhibited fewer breathing episodes on GDs 115-135. Biometrics measures indicated growth retardation in one moderately deprived fetus. These data suggest that moderate, but not marginal, dietary zinc deprivation influences fetal status as evaluated by sonography.

Animals↗
PubMed1991

Maternal versus infant factors related to breast milk intake and residual milk volume: the DARLING study.

Factors related to milk volume and sources of variance in intake were examined using data at 3 months from the longitudinal Davis Area Research on Lactation, Infant Nutrition and Growth study. Milk intake of 73 exclusively breast-fed infants was measured by 4-day test-weighing, correcting for insensible water loss. Total volume extracted was assessed by a combination of test-weighing and expression of breast contents during a subsequent 24-hour period. Residual milk volume was calculated as volume extracted minus intake. Intake, volume extracted, and residual milk volume averaged 818, 914, and 109 g/d, respectively. The interindividual coefficient of variation in intake (16.3%) was greater than within-individual day-to-day variation (8.9%). In comparing those with low (less than 650 g/d) vs average intake, there was no significant difference in residual milk volume between groups (85 vs 111 g/d), indicating that infants with low intakes left as much milk unconsumed as those with higher intakes. There were no differences between groups in maternal age, parity, or anthropometric indices. Infants with low intakes were smaller and spent less time nursing, even though their mothers reportedly nursed on demand. In linear regressions, none of the maternal variables was significantly correlated with intake, volume extracted, or residual milk volume. Infant birth weight, weight at 3 months, and total time nursing were positively associated with intake. The results suggest that infant demand is the main determinant of lactation performance in populations such as this.

Adult↗
PubMed1990

Lactation performance of exercising women.

To determine whether vigorous exercise affects lactation performance, we compared well-nourished exercising (n = 8) and sedentary (n = 8) women whose infants were 9-24 wk old and exclusively breast-fed. Measurements included resting metabolic rate (RMR); maximum oxygen consumption (VO2max); plasma prolactin, cortisol, insulin, and T3; and body composition. Each subject completed a 3-d record of dietary intake, physical activity, and milk volume (by test weighing) and collected 24-h milk samples. Exercising women differed significantly from control subjects in VO2max (46.4 vs 30.3 mL.kg-1.min-1), percent body fat (21.7 vs 27.9%), total energy expenditure (3169 vs 2398 kcal/d), and energy intake (2739 vs 2051 kcal/d). There was no difference between the groups in plasma hormones or milk energy, lipid, protein, or lactose content. Exercising subjects tended to have higher milk volume (839 vs 776 g/d) and energy output in milk (538 vs 494 kcal/d). Thus, there was no apparent adverse effect of vigorous exercise on lactation performance.

Adult↗
PubMed1985

Dietary factors affecting trace element bioavailability from human milk, cow's milk and infant formulas.

Bioavailability of trace elements is affected by the type of diet in which they are presented. In general, absorption of the elements iron, zinc, copper, manganese and selenium appears to be higher from human milk than from cow's milk or cow's milk formula while absorption from soy formula appears to be lower than from milk-based products. The effects of individual components such as protein source, carbohydrate, phytate, organic acids and other cations on absorption need to be assessed and the integrated effects of individual dietary components need to be assessed in the intact diet. While ideally absorptive studies should be performed in human infants, there is a need for developing useful and valid models for assessing trace element bioavailability. Increased knowledge about trace element absorption from different infant diets and the factors involved will lead to a better understanding of trace element requirements of infants. This will help in the suggestion of ways to improve means of supplementation.

Animals↗
PubMed1983

Isolation of specific peptides from Mycobacterium paratuberculosis protoplasm and their use in an enzyme-linked immunosorbent assay for the detection of paratuberculosis (Johne's disease) in cattle.

An antigen was isolated from the protoplasm of Mycobacterium paratuberculosis by a combination of gel filtration, ion exchange, and affinity chromatography. The purified antigen constituted 7.8% of the total protein in the protoplasm. The specificity and sensitivity of the enzyme-linked immunosorbent assay (ELISA) for paratuberculosis, using the purified antigen, were evaluated with sera from 104 cattle which were examined (surveyed) for M paratuberculosis infection by fecal cultural technique. The ELISA was positive in 50 of 60 infected animals. Five of 44 noninfected animals were also test-positive. When a crude protoplasmic extract was used as antigen in the ELISA, sera from 37 infected and from 18 noninfected animals were test-positive. Cross-reactions were encountered in both complement-fixation test and the ELISA between crude or partially purified M paratuberculosis antigens and antisera to Nocardia asteroides, M avium, M phlei, and M fortuitum. The purified antigen gave no complement-fixation reaction with any of these antisera. In the ELISA, cross-reaction was not found when purified antigen was used and the sera were screened at 1:40 dilution.

Animals↗