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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we evidenced a B --> Z helical change in Alzheimer's brain genomic DNA, leading to a hypothesis that Alzheimer's disease (AD) etiological factors such as aluminum (Al), amyloid beta (Abeta) peptide, and Tau might play a role in modulating DNA topology. In the present study, we investigated the interaction of Al and Abeta with DNA. Our results show that Abeta(1-42) could induce a B --> Psi (Psi) conformational change in pUC 18 supercoiled DNA (scDNA), Abeta(1-16) caused an altered B-form, whereas Al induced a complex B-C-A mixed conformation. Ethidium bromide binding and agarose gel electrophoresis studies revealed that Al uncoiled the DNAto a fully relaxed form, whereas Abeta(1-42) and Abeta(1-16) effected a partial uncoiling and also showed differential sensitivity toward chloroquine-induced topoisomer separation. Our findings show for the first time that Abeta and Al modulate both helicity and superhelicity in scDNA. A new hypothetical model explaining the potential toxicity of Abeta and Al in terms of their DNA binding properties leading to DNA conformational alteration is proposed.
J Mol Neurosci 2004
PMID:First evidence for helical transitions in supercoiled DNA by amyloid Beta Peptide (1-42) and aluminum: a new insight in understanding Alzheimer's disease. 1474 7

Methylation events play a critical role in the ability of growth factors to promote normal development. Neurodevelopmental toxins, such as ethanol and heavy metals, interrupt growth factor signaling, raising the possibility that they might exert adverse effects on methylation. We found that insulin-like growth factor-1 (IGF-1)- and dopamine-stimulated methionine synthase (MS) activity and folate-dependent methylation of phospholipids in SH-SY5Y human neuroblastoma cells, via a PI3-kinase- and MAP-kinase-dependent mechanism. The stimulation of this pathway increased DNA methylation, while its inhibition increased methylation-sensitive gene expression. Ethanol potently interfered with IGF-1 activation of MS and blocked its effect on DNA methylation, whereas it did not inhibit the effects of dopamine. Metal ions potently affected IGF-1 and dopamine-stimulated MS activity, as well as folate-dependent phospholipid methylation: Cu(2+) promoted enzyme activity and methylation, while Cu(+), Pb(2+), Hg(2+) and Al(3+) were inhibitory. The ethylmercury-containing preservative thimerosal inhibited both IGF-1- and dopamine-stimulated methylation with an IC(50) of 1 nM and eliminated MS activity. Our findings outline a novel growth factor signaling pathway that regulates MS activity and thereby modulates methylation reactions, including DNA methylation. The potent inhibition of this pathway by ethanol, lead, mercury, aluminum and thimerosal suggests that it may be an important target of neurodevelopmental toxins.
Mol Psychiatry 2004 Apr
PMID:Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal. 1511 82

New and exciting developments in boron research in the past few years greatly contributed to better understanding of the role of boron in plants. Purification and identification of the first boron-polyol transport molecules resolved much of the controversy about boron phloem mobility. Isolation and characterization of the boron-polysaccharide complex from cell walls provided the first direct evidence for boron crosslinking of pectin polymers. Inhibition and recovery of proton release upon boron withdrawal and restitution in plant culture medium demonstrated boron involvement in membrane processes. Rapid boron-induced changes in membrane function could be attributed to boron-complexing membrane constituents. Boron may affect metabolic pathways by binding apoplastic proteins to cis-hydroxyl groups of cell walls and membranes, and by interfering with manganese-dependent enzymatic reactions. In addition, boron has been implicated in counteracting toxic effects of aluminum on root growth of dicotyledonous plants. Molecular investigations of boron nutrition have been initiated by the discovery of a novel mutant of Arabidopsis thaliana with an altered requirement for boron.
Annu Rev Plant Physiol Plant Mol Biol 1998 Jun
PMID:BORON IN PLANT STRUCTURE AND FUNCTION. 1501 43

Oxidant-mediated damage and the triggering of oxidant-sensitive transcription factors could be associated with the neurotoxic actions of aluminum, zinc and lead. Aluminum and lead could induce oxidative stress through their capacity to interact with active oxygen species, increasing their oxidant activity, or by affecting membrane rheology. Aluminum-membrane interactions can also affect signaling cascades. Zinc, at high and low concentrations, increases cell oxidant concentrations, affects AP-1 and NF-kappaB transcription factors and induces neuronal cell death. The capacity of lead to promote oxidative stress, affect cell signals and to induce cell death by apoptosis has been mostly attributed to its effect on different calcium-mediated cellular events. The mentioned mechanisms as well as the contribution of these metals to different neurodegenerative disorders are discussed.
Mol Aspects Med
PMID:Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors. 1505 20

In this paper, the photoluminescence (PL) of porous anodized aluminum oxide (AAO) impregnated with essentially nonfluorescent morin and morin-bovine serum albumin (BSA) was investigated for the first time, respectively. The evident PL bands similar to that of morin-Al3+ complex in solution were observed and the intensity of the latter with morin-BSA was much greater than that of the former with only morin. Moreover, the enhancement increased with the larger pore diameter of the AAO membranes. The appearance of PL bands might be ascribed to the formation of morin-Al complexes in the AAO pores with its inner wall involved. A likely orderly luminescent model was proposed to be responsible for the observed enhancing phenomena of PL due to the coexistence of morin and BSA in the AAO pores.
Spectrochim Acta A Mol Biomol Spectrosc 2004 Apr
PMID:Enhanced photoluminescence of morin-bovine serum albumin on porous anodized aluminum oxide. 1508 18

We have taken a systematic genetic approach to study the potential role of glutathione metabolism in aluminum (Al) toxicity and resistance, using disruption mutants available in Saccharomyces cerevisiae. Yeast disruption mutants defective in phospholipid hydroperoxide glutathione peroxidases (PHGPX; phgpx1 Delta, phgpx2 Delta, and phgpx3Delta), were tested for their sensitivity to Al. The triple mutant, phgpx1 Delta/2Delta/3Delta, was more sensitive to Al (55% reduction in growth at 300 microM Al) than any single phgpx mutant, indicating that the PHGPX genes may collectively contribute to Al resistance. The hypersensitivity of phgpx3Delta to Al was overcome by complementation with PHGPX3, and all PHGPX genes showed increased expression in response to Al in the wild-type strain (YPH250), with maximum induction of approximately 2.5-fold for PHGPX3. Both phgpx3Delta and phgpx1Delta/2Delta/3Delta mutants were sensitive to oxidative stress (exposure to H(2)O(2) or diamide). Lipid peroxidation was also increased in the phgpx1Delta/2Delta/3Delta mutant compared to the parental strain. Disruption mutants defective in genes for glutathione S-transferases (GSTs) (gtt1Delta and gtt2Delta), glutathione biosynthesis (gsh1Delta and gsh2Delta), glutathione reductase (glr1Delta) and a glutathione transporter (opt1Delta) did not show hypersensitivity to Al relative to the parental strain BY4741. Interestingly, a strain deleted for URE2, a gene which encodes a prion precursor with homology to GSTs, also showed hypersensitivity to Al. The hypersensitivity of the ure2Delta mutant could be overcome by complementation with URE2. Expression of URE2 in the parental strain increased approximately 2-fold in response to exposure to 100 microM Al. Intracellular oxidation levels in the ure2Delta mutant showed a 2-fold (non-stressed) and 3-fold (when exposed-to 2 mM H(2)O(2)) increase compared to BY4741; however, the ure2Delta mutant showed no change in lipid peroxidation compared to the control. The phgpx1Delta/2Delta/3Delta and ure2Delta mutants both showed increased accumulation of Al. These findings suggest the involvement of PHGPX genes and a novel role of URE2 in Al toxicity/resistance in S. cerevisiae.
Mol Genet Genomics 2004 Jun
PMID:Reverse genetic analysis of the glutathione metabolic pathway suggests a novel role of PHGPX and URE2 genes in aluminum resistance in Saccharomyces cerevisiae. 1513 56

1. Abundant data suggest that aluminum (Al(III)) exposure may be an environmental risk factor contributing to the development, progression and/or neuropathology of several human neurodegenerative disorders, including Alzheimer's disease (AD). 2. Nuclei appear to be one directed target for Al(III) binding, accumulation, and Al(III)-mediated dysfunction due in part to their high content of polyphosphorylated nucleic acids, nucleotides, and nucleoproteins. 3. The design of chelation therapies dealing with the removal of Al(III) from these genetic compartments therefore represents an attractive strategy to alleviate the development and/or progression of central nervous system dysfunction that may arise from excessive Al(III) exposure. 4. In this study we have investigated the potential application of 10 natural and synthetic Al(III) chelators, including ascorbate (AS), desferrioxamine (DF), and Feralex-G (FG), used either alone or in combination, to remove Al(III) preincubated with intact human brain cell nuclei. 5. Although nuclear bound Al(III) was found to be highly refractory to removal, the combination of AS+FG was found to be particularly effective in removing Al(III) from the nuclear matrix. 6. Our data suggest that chelators carrying cis-hydroxy ketone groups, such as FG, are particularly suited to the removal of Al(III) from complex biological systems. 7. We further suggest a mechanism whereby small chelating molecules may penetrate the nucleus, bind Al(III), diffuse to regions accessible by the larger DF or FG molecules and transfer their Al(III) to DF or FG. 8. The proposed mechanism, called molecular shuttle chelation may provide a useful pharmacotherapy in the potential treatment of Al(III) overload disease.
Cell Mol Neurobiol 2004 Jun
PMID:Molecular shuttle chelation: the use of ascorbate, desferrioxamine and Feralex-G in combination to remove nuclear bound aluminum. 1520 24

The potential of Raman spectroscopy in the quantitative analysis of dilute organic contaminants on aluminum substrates is evidenced in this work. Methyl-parathion microdroplets, an organophosphorus pesticide, has been used as a probe for this purpose. The samples were analyzed on an aluminum foil, which is very easy to acquire and to adapt. Moreover, aluminum foil does not need a previous treatment. Linear and no-linear curves as a function of the concentration of methyl-parathion versus the Raman intensity of the 1345 and 1110 cm(-1) peaks were established by means of a simple mathematical expression. A comparison with calibration curves fits very well, allowing quantification at concentration levels as low as parts per million.
Spectrochim Acta A Mol Biomol Spectrosc 2004 Aug
PMID:Quantitative NIR-Raman analysis of methyl-parathion pesticide microdroplets on aluminum substrates. 1524 10

The structure, stability and molar absorptivity of the complex formed between AlCl(3) and 5,7-dihydroxy-flavone in methanol were investigated using UV-Vis spectroscopy and the AM1 method. The molar ratio method and Job's method of continuous variation were applied to ascertain the stoichiometric composition of the complex in methanol at constant ionic strength. A 1:2 complex was indicated by both methods. The molar absorptivity and stability constant of the complex were determined using a simple and accurate procedure that requires solutions having the ligand and metal ion in the stoichiometric proportion. The high stability constant demonstrates that the complexation reaction is total. The structure of this complex, obtained by the quantum semi-empirical AM1 method, indicates that two classes of metal-ligand interactions are involved in the formation of the metal complex: (a) two simple covalent bonds between the aluminum atom and the oxygen atoms of o-hydroxyl groups of 5,7-dihydroxy-flavone; (b) two stronger Coulombic interactions between the aluminum atom and the carbonyl oxygen atoms of the ligand.
Spectrochim Acta A Mol Biomol Spectrosc 2004 Aug
PMID:Structural and spectroscopic study of 5,7-dihydroxy-flavone and its complex with aluminum. 1524 11

When intracisternally injected to rat brain, aluminum induced apoptosis as assessed by DNA fragmentation and activation of caspase-3 and caspase-12. Co-administration of glial cell line-derived neurotrophic factor (GDNF) effectively prevented aluminum-induced cell death through reduced apoptosis whereas brain-derived neurotrophic factor (BDNF) accelerated aluminum-induced apoptosis, suggesting that the extent of aluminum neurotoxicity in vivo may depend on the biological activity of the neurotrophic factors.
Brain Res Mol Brain Res 2004 Aug 23
PMID:Opposed regulation of aluminum-induced apoptosis by glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor in rat brains. 1530 32


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