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At least 1,207 records · Page 67Linked to original sources
PubMed1996

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Kidney cortex is a main target for circulating vitamin B12 (cobalamin) in complex with transcobalamin (TC). Ligand blotting of rabbit kidney cortex with rabbit 125I-TC-B12 and human TC-57Co-B12 revealed an exclusive binding to megalin, a 600-kDa endocytic receptor present in renal proximal tubule epithelium and other absorptive epithelia. The binding was Ca2+ dependent and inhibited by receptor-associated protein (RAP). Surface plasmon resonance analysis demonstrated a high-affinity interaction between purified rabbit megalin and rabbit TC-B12 but no measurable affinity of the vitamin complex for the homologous alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor related protein (LRP). 125I-TC-B12 was efficiently endocytosed in a RAP-inhibitable manner in megalin-expressing rat yolk sac carcinoma cells and in vivo microperfused rat proximal tubules. The radioactivity in the tubules localized to the endocytic compartments and a similar apical distribution in the proximal tubules was demonstrated after intravenous injection of 125I-TC-B12. The TC-B12 binding sites in the proximal tubule epithelium colocalized with megalin as shown by ligand binding to cryosections of rat kidney cortex, and the binding was inhibited by anti-megalin polyclonal antibody, EDTA, and RAP. These data show a novel nutritional dimension of megalin as a receptor involved in the cellular uptake of vitamin B12. The expression of megalin in absorptive epithelia in the kidney and other tissues including yolk sac and placenta suggests a role of the receptor in vitamin B12 homeostasis and fetal vitamin B12 supply.

Animals↗
PubMed1997

YY1 regulates vitamin D receptor/retinoid X receptor mediated transactivation of the vitamin D responsive osteocalcin gene.

The responsiveness of genes to steroid hormones is principally mediated by functional interactions between DNA-bound hormone receptors and components of the transcriptional initiation machinery, including TATA-binding protein, TFIIB, or other RNA polymerase II associated factors. This interaction can be physiologically modulated by promoter context-specific transcription factors to facilitate optimal responsiveness of gene expression to hormone stimulation. One postulated regulatory mechanism involves the functional antagonism between hormone receptors and nonreceptor transcription factors interacting at the same hormone response element. Here we demonstrate that the multifunctional regulator YY1 represses 1,25-dihydroxyvitamin D3 (vitamin D)-induced transactivation of the bone tissue-specific osteocalcin gene. We identify YY1 recognition sequences within the vitamin D response element (VDRE) of the osteocalcin gene that are critical for YY1-dependent repression of vitamin D-enhanced promoter activity. We show that YY1 and vitamin D receptor (VDR)/retinoid X receptor heterodimers compete for binding at the osteocalcin VDRE. In addition, we find that YY1 interacts directly with TFIIB, and that one of the two tandemly repeated polypeptide regions of TFIIB spanning the basic domain is responsible for this interaction. TFIIB and VDR can also interact directly, and these factors synergize to mediate transactivation. Our results suggest that YY1 regulates vitamin D enhancement of osteocalcin gene transcription in vivo by interfering with the interactions of the VDR with both the VDRE and TFIIB.

Animals↗
PubMed1997

Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia.

Vitamin D, the major steroid hormone that controls mineral ion homeostasis, exerts its actions through the vitamin D receptor (VDR). The VDR is expressed in many tissues, including several tissues not thought to play a role in mineral metabolism. Studies in kindreds with VDR mutations (vitamin D-dependent rickets type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets, and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is seen in some kindreds. We have generated a mouse model of VDDR II by targeted ablation of the second zinc finger of the VDR DNA-binding domain. Despite known expression of the VDR in fetal life, homozygous mice are phenotypically normal at birth and demonstrate normal survival at least until 6 months. They become hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH) levels begin to rise. Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets and osteomalacia are seen by day 35; however, as early as day 15, there is an expansion in the zone of hypertrophic chondrocytes in the growth plate. In contrast to animals made vitamin D deficient by dietary means, and like some patients with VDDR II, these mice develop progressive alopecia from the age of 4 weeks.

Alopecia↗
PubMed1999

The propeptides of the vitamin K-dependent proteins possess different affinities for the vitamin K-dependent carboxylase.

The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the modification of specific glutamates in a number of proteins required for blood coagulation and associated with bone and calcium homeostasis. All known vitamin K-dependent proteins possess a conserved eighteen-amino acid propeptide sequence that is the primary binding site for the carboxylase. We compared the relative affinities of synthetic propeptides of nine human vitamin K-dependent proteins by determining the inhibition constants (Ki) toward a factor IX propeptide/gamma-carboxyglutamic acid domain substrate. The Ki values for six of the propeptides (factor X, matrix Gla protein, factor VII, factor IX, PRGP1, and protein S) were between 2-35 nM, with the factor X propeptide having the tightest affinity. In contrast, the inhibition constants for the propeptides of prothrombin and protein C are approximately 100-fold weaker than the factor X propeptide. The propeptide of bone Gla protein demonstrates severely impaired carboxylase binding with an inhibition constant of at least 200,000-fold weaker than the factor X propeptide. This study demonstrates that the affinities of the propeptides of the vitamin K-dependent proteins vary over a considerable range; this may have important physiological consequences in the levels of vitamin K-dependent proteins and the biochemical mechanism by which these substrates are modified by the carboxylase.

Amino Acid Sequence↗
PubMed1985

Vitamin B12 absorption in the neonatal piglet. 2. Resistance of the vitamin B12-binding protein in sows' milk to proteolysis in vivo.

It has been postulated that the vitamin B12-binding protein in the sows' milk may facilitate the intestinal absorption of vitamin B12 in the piglet. This implies that the binder is not rapidly and completely degraded by gut proteases, and the present experiments were devised to test this assumption. Piglets aged 7 and 28 d were given a test feed of sows' milk whey both with and without cyano[3H]cobalamin to saturate the binder, and with 14C-labelled polyethylene glycol (PEG) as a marker. Control piglets were given a milk substitute containing no vitamin B12-binder. At 80 min after the test meal the piglets were killed and the contents of the stomach and small intestine were removed for analysis. Recovery of [14C]PEG, mainly from the middle and distal portions of the small intestine, ranged from 49 to 78%. Apparent loss of vitamin B12-binder from the intestine was calculated from the ratio, PEG:binder. In both 7- and 28-d-old piglets, the content of saturated binder in the middle and lower small intestine was about 20% depleted relative to that in the test fed. With the unsaturated binder the loss was more variable and generally greater, at about 50%. At slaughter the stomach was nearly empty and the high unsaturated binding capacity of the contents was attributed to endogenous binders. However, in the middle and lower small intestine, the binding capacity was derived mainly from sows' milk given with the test meal. No free cyano[3H]cobalamin was found in the intestinal contents of piglets given sows' milk to which enough cyano[3H]cobalamin had been added to saturate the binder. There was no change in the molecular weight of the vitamin B12-binder during its passage down the intestine, as judged by its behaviour on filtration in Sephadex gel G-150. The results indicate that a high proportion of saturated binder, and a smaller proportion of unsaturated binder, survived unchanged in the intestine of piglets at both ages.

Absorption↗
PubMed2004

Antioxidant effects of taurine, vitamin C, and vitamin E on oxidative damage in hippocampus caused by the administration of 3-nitropropionic acid in rats.

The administration of 3-nitropropionic acid increases reactive oxygen species (ROS). Antioxidant defense mechanisms buffer these ROS converting them into non-damaging compounds. Taurine and vitamins C and E are antioxidants that play a role in the defense against cellular damage. This study examines the antioxidant effect of taurine, vitamin C, and vitamin E on acute hippocampal damage caused by 3-NP. Animals treated with 3-NP increased lipid peroxidation levels and astrocytic damage in the hippocampus. Administration of taurine, vitamin C, and vitamin E partially protected from oxidative damage, indicate that while all substances had antioxidant effects, only taurine showed morphological protection in surviving cells.

Animals↗
PubMed1989

Vitamin A concentrations in liver determined by isotope dilution assay with tetradeuterated vitamin A and by biopsy in generally healthy adult humans.

The vitamin A status in 11 generally healthy surgical patients was estimated by measuring the dilution of a 45-mg oral dose of tetradeuterated retinyl acetate (99% pure). After purification of retinol by high-performance liquid chromatography, the ratio of 2H4-retinol:1H-retinol in plasma was measured by gas chromatography-mass spectrometry. On the basis of the observed ratios of [2H4]retinol:[1H]retinol over 19-47 d, the total body reserves and liver concentrations of vitamin A were calculated. Liver biopsy samples taken at surgery were directly analyzed for vitamin A. The correlation coefficient between calculated and measured liver vitamin A concentrations for 10 of the subjects was 0.88, and the Spearman's rank correlation coefficient was 0.95 (p less than 0.002). Thus, total body reserves of vitamin A in humans can be estimated validly in the marginal and satisfactory ranges by a benign, relatively noninvasive procedure.

Adult↗
PubMed1989

Vitamin E status of northern Canadian newborns: relation of vitamin E to blood lipids.

Vitamin E status was determined in two groups of Canadian newborns: a northern group, mainly aboriginal (Indian and Inuit), and a southern group, mainly nonnative. Serum vitamin E, cholesterol, and triglyceride levels were measured in cord blood and ratios of vitamin E to both cholesterol (E:chol) and cholesterol plus triglyceride (E:chol + TG) were calculated. For the combined groups the mean serum concentration of vitamin E (8.71 +/- 2.45 mumol/L), cholesterol (1.77 +/- 0.46 mmol/L), and triglyceride (0.65 +/- 0.30 mmol/L) as well as the ratios E:chol (5.00 X 10(-3) +/- 1.26 X 10(-3) and E:chol + TG (3.60 X 10(-3) +/- 0.77 X 10(-3) were within normal limits. Significant north-south differences were found only in the mean triglyceride concentration, which was lower (p = 0.03), and E:chol + TG, which was higher (p = 0.002), in the northern than in the southern group. No differences attributable to differences in race were found. Only one infant, an Inuit in the northern group, was found to be deficient in vitamin E.

Adult↗
PubMed1992

Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease.

We evaluated vitamin A absorption in 50 healthy adults and 26 gastrointestinal-disease patients by measuring the postabsorptive response in plasma retinyl esters after oral doses of the vitamin. On 3 consecutive days, two physiologic-dose tests of 2000-2400 retinol equivalents (RE) and one pharmacologic-dose test (84,000 RE) were administered. The physiologic doses were given as an oil-soluble or a water-miscible preparation. In gastrointestinal-disease patients the physiologic-dose test was highly correlated with the pharmacologic-dose test for the oil-soluble preparation as determined by peak rise (r = 0.50, P less than 0.05) and area under the curve (r = 0.56, P less than 0.01), suggesting that the physiologic dose is valid for investigating vitamin A absorption. Intestinal-disease or resection patients absorbed preparations poorly. Pancreatic-disease patients absorbed the oil-soluble preparation poorly. Physiologic rather than pharmacologic doses of vitamin A can be used to study vitamin A absorption.

Absorption↗
PubMed1994

Efficacy of water-soluble vitamin E in the treatment of vitamin E malabsorption in short-bowel syndrome.

A water-soluble form of vitamin E, tocopheryl succinate polyethylene glycol 1000 (TPGS), was used as an oral vitamin E supplement in a 71-y-old patient with severe fat malabsorption and vitamin E deficiency secondary to short-bowel syndrome. An absorption test with deuterium-labeled TPGS demonstrated that TPGS was absorbed and the released alpha-tocopherol was transported normally in lipoproteins. The disappearance portion of the deuterated alpha-tocopherol curves were parallel to those in control subjects, suggesting normal metabolic turnover of alpha-tocopherol. Long-term (3 y) supplementation with orally administered TPGS (10,360 mg or 4000 IU/d) maintained normal plasma alpha-tocopherol concentrations, raised adipose tissue alpha-tocopherol concentrations, and prevented further progression of the neurological abnormalities resulting from vitamin E deficiency. Thus, TPGS can be an effective vitamin E supplement in short-bowel syndrome despite severe fat malabsorption.

Aged↗
PubMed1996

Daily supplements of vitamin A (8.4 mumol, 8000 IU) improve the vitamin A status of lactating Indonesian women.

The vitamin A statuses of lactating Indonesian women (n = 23) starting at 1-3 mo after delivery were determined at three monthly intervals (times 1, 2, and 3) during lactation and then again (time 4) after they had ingested vitamin A capsules (8.4 mumol, 8000 IU) daily for 35 d. Vitamin A status was determined by using the modified-relative-dose-response (MRDR) test and serum retinol concentrations. The mean MRDR ratio in these women rose from 0.084 +/- 0.047 (time 1) to 0.099 +/- 0.045 (time 2) and then to 0.100 +/- 0.054 (time 3). After supplementation the mean MRDR ratio fell to 0.040 +/- 0.021 (time 4) (P < 0.0001). Mean serum retinol concentrations at the first three times were 0.94 +/- 0.23, 0.87 +/- 0.20, and 0.80 +/- 0.20 mumol/L, but then rose to 1.10 +/- 0.31 mumol/L at time 4 (P < 0.04). After supplementation mean MRDR values and mean serum retinol concentrations were 60% lower and 38% higher, respectively, than those just before supplementation, MRDR values better distinguished the vitamin A statuses of the women than did serum retinol concentrations. Mean hemoglobin values increased during the study from 118 +/- 9 g/L at time 1 to 122 +/- 6 g/L at time 4 (P = 0.0187). The mean hematocrit also rose from 0.35 +/- 0.03 at time 1 to 0.361 +/- 0.17 at time 4 (P = 0.0478). Thus, iron status may also have improved marginally from time 1 to time 4, but most of the increase appeared before the vitamin A intervention.

Adolescent↗
PubMed1999

Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study.

In a randomized, placebo-controlled, double-blind study we investigated whether high-dose oral treatment with vitamins C and E for 56 days was able to improve semen parameters of infertile men. Ejaculate parameters included semen volume, sperm concentration and motility, and sperm count and viability. Thirty-one patients without genital infection but with asthenozoospermia (< 50% motile spermatozoa) and normal or only moderately reduced sperm concentration (> 7 x 10(6) spermatozoa/ml) (according to WHO criteria) were examined. To investigate the influence of the epididymal storage period on semen parameters, the patients were asked to deliver two semen samples with abstinence times of 2 and 7 days both before and at the end of vitamin treatment. After randomization, the patients received either 1000 mg vitamin C and 800 mg vitamin E (n = 15) or identical placebo capsules (n = 16). No changes in semen parameters were observed during treatment, and no pregnancies were initiated during the treatment period. Combined high-dose antioxidative treatment with vitamins C and E did not improve conventional semen parameters or the 24-h sperm survival rate. Prolonged abstinence time increased ejaculate volume (P < 0.05), sperm count (P < 0.05), sperm concentration (P < 0.05) and the total number of motile spermatozoa (P < 0.05).

Administration, Oral↗
PubMed1976

Influence of pyridoxine supplementation on vitamin B-6 levels in milk of rats deficient in the vitamin.

Levels of vitamin B-6 in milk from pyridoxine deficient dams were used as an indicator of the ability of pyridoxine to protect offspring against the effects of the deficiency. Sprague Dawley rats were fed a basal diet containing 30.0 (control) or 1.2 (deficient) mg pyridoxine-HC1/kg diet from weaning throughout growth, gestation and until 5 days postpartum. At this time, deficient dams were supplemented by a single intraperitoneal injection of 600 mug pyridoxine-HC1, or by adding 30 or 60 mg pyridoxine-HC1/kg to the diet. The vitamin B-6 content in milk form the group supplemented by injection exceeded the control level of 38.8 mug/100 ml milk 30 minutes after the injection, and reached a peak level of 110.7 mug/100 ml at 4 hours with a subsequent decline to 27mug/100 ml at 20 hours. In rats supplemented orally with 30 or 60 mg pyridoxine-HC1/kg diet, the vitamin B-6 level in the milk reached the control value in 24 and 6 hours, respectively. At 120 hours, orally supplemented dams had significantly higher levels of vitamin B-6 in the milk than control animals. Vitamin supplementation of dams by a single injection of pyridoxine-HC1 was sufficient to overcome the pyridoxine deficiency syndrome in the pups, but was not adequate for optimum growth.

Animals↗
PubMed1983

Transfer of vitamin A from intestine to plasma in lambs fed low and high intakes of vitamin A.

Three groups of lambs were fed a low carotene diet supplemented with vitamin A proprionate equivalent to 0, 100 or 12,000 micrograms retinol per kilogram per day via rumen cannulae. These groups were mildly deficient, normal (control) and intoxicated, respectively. After 17 weeks, abomasal cannulae were implanted, [15-3H]retinol was injected into the abomasum, and jugular blood was sampled for 48 hours. After 7 days, the tracer was injected into a jugular vein, and blood was sampled for 48 hours. Rates of retinol and retinyl ester transport and retinol clearance from plasma reflected intake (P less than 0.05); clearance of retinyl esters was unaffected. Mean efficiencies of total vitamin A (retinol and retinyl ester) transfer from digestive tract to plasma were 86, 60 and 60%, whereas those of retinol were 91, 58 and 14% (P less than 0.05) for mildly deficient, control and intoxicated lambs, respectively. Thus lower transfer efficiencies were associated with higher transport rates of plasma retinol and retinyl ester and with increased clearance of retinol but not retinyl ester from plasma. These results suggest that vitamin A transfer from intestine to plasma is sensitive to vitamin A intake, and that retinol is the primary form of vitamin A affected.

Animals↗
PubMed2000

The function of vitamin D receptor in vitamin D action.

Vitamin D has roles in a variety of biological actions such as calcium homeostasis, cell proliferation and cell differentiation to many target tissues. Most of these biological actions of vitamin D are now considered to be exerted through the nuclear vitamin D receptor (VDR)-mediated control of target genes. VDR belongs to the nuclear hormone receptor superfamily and acts as a ligand-inducible transcription factor. For the ligand-induced transactivation of VDR, coactivator complexes have recently been shown to be essential. The function of VDR as a ligand-induced transcription factor is overviewed, and the phenotype of VDR gene knock-out mice and the VDR-mediated transcriptional and negative regulation of the key enzyme in vitamin D biosynthesis are also described, based mainly on our recent findings, to gain a better understanding of the function of VDR in the transcriptional control of vitamin D target genes.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1995

Functional improvement with vitamin D replenishment in a cohort of frail, vitamin D-deficient older people.

OBJECTIVE: To evaluate functional improvement in a population of frail, homebound older persons with low vitamin D status as vitamin D stores improve. DESIGN: Randomized, controlled intervention study. SETTING: Subjects' homes and a nursing facility in Baltimore, Maryland. PARTICIPANTS: The first 32 subjects (community-dwelling, homebound older subjects from the Johns Hopkins Elder Housecall Program and nursing home residents from the Johns Hopkins Geriatrics Center) entered in a longitudinal study of vitamin D replacement. MEASUREMENTS: Baseline 25-hydroxyvitamin D levels were measured and repeated at least 1 month after therapy with either placebo or vitamin D (ergocalciferol). Subjects were also administered the Frail Elderly Functional Assessment (FEFA) questionnaire, an instrument demonstrated to be reliable, valid, and sensitive to small increments of functional change in this population. MAIN RESULTS: All subjects started with 25-hydroxyvitamin D levels less than 15 ng/mL. Those subjects whose levels improved by at least 3 ng/mL (> assay coefficient of variation) also demonstrated improvement in FEFA score. Regression analysis between change in FEFA score compared with change in 25-hydroxyvitamin D was significant (r = .4; P = .02). CONCLUSIONS: In this cohort of homebound older people, improvement in vitamin D status was associated with functional improvement as measured by the FEFA questionnaire.

Aged↗
PubMed1972

Role of third serum vitamin B 12 binding protein in vitamin B 12 transport.

A third vitamin B(12) binding protein present in normal serum has been shown to participate in transport of labelled vitamin B(12) absorbed from the gut. All three vitamin B(12) binding proteins in serum were labelled at the same time after oral administration of vitamin B(12), implying that "free" vitamin B(12) reached the portal blood from the gut mucosa.

Biological Transport↗
PubMed1977

Vitamin D supplements and 25-hydroxy vitamin D concentrations in the elderly.

Serial 25-hydroxy vitamin D (25-OHD) concentrations were measured in long-stay geriatric patients treated with vitamin D. Comparison between a treatment and a control group showed that a daily dose of 500 IU vitamin D produced a significant increase in 25-OHD levels by two months. The supplement had a striking effect when the initial 25-OHD level was low and very little effect when it was high. 25-OHD levels in subjects on 2000 IU vitamin D daily were only marginally higher than those in subjects on 500 IU. A dose of 500 IU vitamin D daily should therefore produce adequate blood 25-OHD concentrations in most old people, and probably prevent most cases of osteomalacia in the elderly--though a large-scale study is needed to confirm this.

Aged↗