Separate and joint effects of micronutrient deficiencies on linear growth.
(9/8763)
Recent studies have investigated the effect of micronutrient deficiencies on growth stunting, with special attention toward the effect of zinc, iron, vitamin A and iodine deficiencies. In Mexico, the prevalence of growth stunting in children <5 y old is approximately 24%; it is higher in rural areas and lower in urban areas. In an initial study, the effect of zinc and/or iron supplementation on linear growth was investigated in a longitudinal, placebo-controlled design. After 12 mo of supplementation, there was no difference between the groups supplemented with zinc, iron or zinc plus iron and the placebo group. At baseline, 82% of the children in this study were deficient in at least two out of the five micronutrients that were determined, and 73% were anemic. In another study, a mixture of those micronutrients that were documented to be lacking in Mexican children was formulated in a supplement and given to Mexican children over a period of 12 mo in a longitudinal, placebo-controlled, supplementation design. Children in the low and medium socioeconomic status grew about 1 cm more than similar children in the placebo group. This difference was not found in children of high socioeconomic status. It is suggested that, in most cases, growth stunting is associated with marginal deficiencies of several micronutrients and that in populations with multiple micronutrient deficiencies, the effect on linear growth of supplementation with single nutrients will not be significant. Supplementation with multiple micronutrients is expected to be more effective, but even in that case the actual increment in height was less than the expected potential increment. (+info)
Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation.
(10/8763)
p21(Cip1/WAF1) inhibits cell-cycle progression by binding to G1 cyclin/CDK complexes and proliferating cell nuclear antigen (PCNA) through its N- and C-terminal domains, respectively. The cell-cycle inhibitory activity of p21(Cip1/WAF1) is correlated with its nuclear localization. Here, we report a novel cytoplasmic localization of p21(Cip1/WAF1) in peripheral blood monocytes (PBMs) and in U937 cells undergoing monocytic differentiation by in vitro treatment with vitamin D3 or ectopic expression of p21(Cip1/WAF1), and analyze the biological consequences of this cytoplasmic expression. U937 cells which exhibit nuclear p21(Cip1/WAF1) demonstrated G1 cell-cycle arrest and subsequently differentiated into monocytes. The latter event was associated with a cytoplasmic expression of nuclear p21(Cip1/WAF1), concomitantly with a resistance to various apoptogenic stimuli. Biochemical analysis showed that cytoplasmic p21(Cip1/WAF1) forms a complex with the apoptosis signal-regulating kinase 1 (ASK1) and inhibits stress-activated MAP kinase cascade. Expression of a deletion mutant of p21(Cip1/WAF1) lacking the nuclear localization signal (DeltaNLS-p21) did not induce cell cycle arrest nor monocytic differentiation, but led to an apoptosis-resistant phenotype, mediated by binding to and inhibition of the stress-activated ASK1 activity. Thus, cytoplasmic p21(Cip1/WAF1) itself acted as an inhibitor of apoptosis. Our findings highlight the different functional roles of p21(Cip1/WAF1), which are determined by its intracellular distribution and are dependent on the stage of differentiation. (+info)
The distribution of zinc selenite and expression of metallothionein-III mRNA in the spinal cord and dorsal root ganglia of the rat suggest a role for zinc in sensory transmission.
(11/8763)
Zinc appears to play a role in synaptic transmission in the hippocampus. We tested the hypothesis that zinc is similarly involved in sensory transmission by determining whether vesicular zinc and metallothionein-III (MT-III), a zinc-binding protein, are localized in rat primary afferent neurons. MT-III mRNA, measured using RT-PCR, and MT-III immunoreactivity, were both present in the spinal cord as well as the thoracic and lumbar dorsal root ganglia (DRG). At a time (24 hr) that allows retrograde transport of zinc selenite to cell bodies, only small-diameter neurons and neurons scattered throughout lamina V of the spinal cord were stained by sodium selenite injected intrathecally. This stain disappeared if a ligature was placed on the dorsal root to block axonal transport, demonstrating that these cells are, in fact, zinc-containing primary afferent neurons. When assessed 1 hr after sodium selenite, stain was distributed throughout the neuropil of the spinal cord, especially in lamina III and the area surrounding the central canal. Even in rhizotomized animals, large- and small-diameter DRG neuronal cell bodies were also stained with either selenite (1 hr) or 6-methoxy 8-para-toluene sulfonamide quinoline (TSQ). Paradoxically, this unique pool of zinc was eliminated in large-diameter DRG neurons after neonatal capsaicin treatment, which had no effect on selenite stain or MT-III mRNA content in small-diameter DRG neurons. In summary, we demonstrate that there is a population of capsaicin-insensitive small-diameter primary afferent neurons that are zinc-containing. In addition, there is a unique pool of capsaicin-sensitive zinc that is associated with large-diameter cell bodies. (+info)
Determining anomericity of the glycosidic bond in Zn(II)-diethylenetriamine-disaccharide complexes using MSn in a quadrupole ion trap.
(12/8763)
Zinc-diethylenetriamine (Zn-dien) N-glycoside complexes of four 1,4 and four 1,6 linked disaccharides are prepared. Each reaction mixture is ionized by electrospray and the resulting species [Zn(dien)(disaccharide)-H]+ is allowed to undergo collision-induced dissociation in a quadrupole ion trap. An MS3 analysis is used to differentiate alpha versus beta anomericity of the glycosidic bond in the disaccharide moiety. In addition, the MS2 and MS3 spectra can be used together to determine the linkage position of this glycosidic bond. (+info)
The Enterococcus hirae copper chaperone CopZ delivers copper(I) to the CopY repressor.
(13/8763)
Expression of the cop operon which effects copper homeostasis in Enterococcus hirae is controlled by the copper responsive repressor CopY. Purified Zn(II)CopY binds to a synthetic cop promoter fragment in vitro. Here we show that the 8 kDa protein CopZ acts as a copper chaperone by specifically delivering copper(I) to Zn(II)CopY and releasing CopY from the DNA. As shown by gel filtration and luminescence spectroscopy, two copper(I) are thereby quantitatively transferred from Cu(I)CopZ to Zn(II)CopY, with displacement of the zinc(II) and transfer of copper from a non-luminescent, exposed, binding site in CopZ to a luminescent, solvent shielded, binding site in CopY. (+info)
GCS1, an Arf guanosine triphosphatase-activating protein in Saccharomyces cerevisiae, is required for normal actin cytoskeletal organization in vivo and stimulates actin polymerization in vitro.
(14/8763)
Recent cloning of a rat brain phosphatidylinositol 3,4, 5-trisphosphate binding protein, centaurin alpha, identified a novel gene family based on homology to an amino-terminal zinc-binding domain. In Saccharomyces cerevisiae, the protein with the highest homology to centaurin alpha is Gcs1p, the product of the GCS1 gene. GCS1 was originally identified as a gene conditionally required for the reentry of cells into the cell cycle after stationary phase growth. Gcs1p was previously characterized as a guanosine triphosphatase-activating protein for the small guanosine triphosphatase Arf1, and gcs1 mutants displayed vesicle-trafficking defects. Here, we have shown that similar to centaurin alpha, recombinant Gcs1p bound phosphoinositide-based affinity resins with high affinity and specificity. A novel GCS1 disruption strain (gcs1Delta) exhibited morphological defects, as well as mislocalization of cortical actin patches. gcs1Delta was hypersensitive to the actin monomer-sequestering drug, latrunculin-B. Synthetic lethality was observed between null alleles of GCS1 and SLA2, the gene encoding a protein involved in stabilization of the actin cytoskeleton. In addition, synthetic growth defects were observed between null alleles of GCS1 and SAC6, the gene encoding the yeast fimbrin homologue. Recombinant Gcs1p bound to actin filaments, stimulated actin polymerization, and inhibited actin depolymerization in vitro. These data provide in vivo and in vitro evidence that Gcs1p interacts directly with the actin cytoskeleton in S. cerevisiae. (+info)
Overexpression of a novel Arabidopsis gene related to putative zinc-transporter genes from animals can lead to enhanced zinc resistance and accumulation.
(15/8763)
We describe the isolation of an Arabidopsis gene that is closely related to the animal ZnT genes (Zn transporter). The protein encoded by the ZAT (Zn transporter of Arabidopsis thaliana) gene has 398 amino acid residues and is predicted to have six membrane-spanning domains. To obtain evidence for the postulated function of the Arabidopsis gene, transgenic plants with the ZAT coding sequence under control of the cauliflower mosaic virus 35S promoter were analyzed. Plants obtained with ZAT in the sense orientation exhibited enhanced Zn resistance and strongly increased Zn content in the roots under high Zn exposure. Antisense mRNA-producing plants were viable, with a wild-type level of Zn resistance and content, like plants expressing a truncated coding sequence lacking the C-terminal cytoplasmic domain of the protein. The availability of ZAT can lead to a better understanding of the mechanism of Zn homeostasis and resistance in plants. (+info)
Effect of alpha-hederin on hepatic detoxifying systems in mice.
(16/8763)
AIM: To examine whether alpha-hederin (Hed) modulates hepatic detoxifying systems as a means of hepatoprotection. METHODS: Mice were injected Hed 10 and 30 mumol.kg-1 sc for 3 d, and liver cytosols were prepared 24 h after the last dose to study antioxidant enzymes and nonenzymatic defense components. RESULTS: Hed increased liver glutathione (GSH) content (20%), but had no effect on GSH peroxidase, GSH reductase, and GSH S-transferase. The activities of superoxide dismutase and quinone reductase were unaffected by Hed treatment. At the high dose of Hed, catalase activity was decreased by 20%. Hepatic content of metallothionein was dramatically increased (50-fold), along with elevations of hepatic Zn and Cu concentrations (25%-80%). Hed also increased ascorbic acid concentration (20%), but no effect on alpha-tocopherol in liver. CONCLUSION: Hed enhanced some nonenzymatic antioxidant components in liver, which play a partial role in Hed protection against hepatotoxicity produced by some chemicals. (+info)