A P-type ATPase importer that discriminates between essential and toxic transition metals.
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ABSTRACT:
SUBMITTER: Lewinson O
PROVIDER: S-EPMC2651836 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: This investigation examines the extraction of metals from animal bones into broth, and assesses whether bone broths are good sources of essential metals and the risks associated with the consumption of toxic metals. Method:Three sets of controlled experiments were performed to study the factors (cooking time, acidity, bone type and animal species) that influence metal extractions. Three types of animal bone broth-based foods were also tested. Results: Reducing the broth pH from 8.38 to 5.32 significantly (p < 0.05) increased Ca and Mg extraction by factors of 17.4 and 15.3, respectively. A long cooking time, > 8 h, yielded significantly higher (p < 0.05) Ca and Mg extraction than shorter cooking times. The extraction characteristics of metals, particularly Ca, Mg, Cu and Al, from the leg and rib bones differed. The between-species variations in extraction were larger than those of within-species. Conclusions:The Ca and Mg levels in home-made or commercial broth/soup were found not to exceed low tenths of milligram per serving, or <5% of the daily recommended levels. The risks that are associated with the ingestion of heavy metals such as Pb and Cd in broth are minimal because the levels were in the ranges of a few μg per serving.
| S-EPMC5533136 | biostudies-other
Project description:IntroductionCerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children.MethodsIn a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses.ResultsThe essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified.ConclusionUsing mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.
| S-EPMC10470125 | biostudies-literature
Project description:FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.
| S-EPMC2956120 | biostudies-other
Project description:BackgroundComprehensive examinations of placental metal concentrations and correlations with infant parameters are under-investigated. Chattanooga, Tennessee's consistently high incidence of low birth weight and potential for metal exposure provides an ideal opportunity to investigate potential correlations.ObjectivesTo investigate the associations between a wide variety of metals in placental tissue and multiple infant parameters.MethodsA total of 31 elements were screened via ICP-MS in 374 individual placental samples. Of those, 14 were quantifiable in > 86% of the samples. We examined correlations between metal concentrations and infant parameters (birth weight, gestational age, birth weight centile, placental weight, birth length and head circumference). We fit multivariable regression models to estimate the covariate-adjusted associations of birth weight with ln-transformed concentrations of each of the 14 metals and used generalized additive models to examine nonlinear relationships.ResultsSome of the strongest relationships with infant parameters came from several lesser-studied metals. Placental rhodium concentrations were negatively correlated with almost all infant parameters. In the fully adjusted regression model, birth weight was significantly associated with several metals. On an IQR (25th to the 75th percentile) basis, estimated changes in birthweight were: for cobalt (82.5 g, IQR=6.05 µg/kg, p = 0.006), iron (-51.5 g, IQR = 171800 µg/kg, p = 0.030), manganese (-27.2 g, IQR=152.1 µg/kg, p = 0.017), lead (-72.7 g, IQR=16.55 µg/kg, p = 0.004) and rhodium (-1365.5 g, IQR = 0.33 µg/kg, p < 0.001). Finally, a generalized additive model showed significant nonlinear relationships between birth weight and concentrations of Co and Rh.ConclusionsOur comprehensive examination of placental metals illustrate many strong associations between lesser-studied metals and infant parameters. These data, in combination with our correlations of well-studied metals, illustrate a need to consider in utero exposure to a broad array of metals when considering fetal development.
| S-EPMC6288679 | biostudies-literature
Project description:The persistent nature of lead (Pb) and cadmium (Cd) in the environment severely affects plant growth and yield. Conversely, plants acquire zinc (Zn) from the soil for their vital physiological and biochemical functions. However, the interplay and coordination between essential and toxic metals for their uptake and translocation and the putative underlying epigenetic mechanisms have not yet been investigated in maize. Here, we report that the presence of Zn facilitates the accumulation and transport of Pb and Cd in the aerial parts of the maize plants. Moreover, the Zn, Pb, and Cd interplay specifically interferes with the uptake and translocation of other divalent metals, such as calcium and magnesium. Zn, Pb, and Cd, individually and in combinations, differentially regulate the expression of DNA methyltransferases, thus alter the DNA methylation levels at the promoter of Zinc-regulated transporters, Iron-regulated transporter-like Protein (ZIP) genes to regulate their expression. Furthermore, the expression of histone deacetylases (HDACs) varies greatly in response to individual and combined metals, and HDACs expression showed a negative correlation with ZIP transporters. Our study highlights the implication of DNA methylation and histone acetylation in regulating the metal stress tolerance dynamics through Zn transporters and warns against the excessive use of Zn fertilizers in metal contaminated soils.
| S-EPMC7555519 | biostudies-literature
Project description:Early-life exposure to heavy metals and/or trace metal imbalances can have negative developmental effects. Here we sought to characterize exposure profiles for 20 heavy metals and trace elements in umbilical cord blood plasma and identify demographic predictors of exposure. Twenty metals were measured in cord plasma from 357 Chinese infants using ICP-MS. Relationships between demographic variables and metals were analyzed using generalized linear models and logistic regression. Ten metals (antimony [Sb], cobalt [Co], cesium [Cs], copper [Cu], lead [Pb], molybdenum [Mo], rubidium [Rb], selenium [Se], strontium [Sr], titanium [Ti], zinc [Zn]) were detected in all samples. Season of birth was the strongest predictor of metals in cord blood across analyses. Infants born in the spring had 0.1-0.2??g L-1 higher logAs and logCo in their cord blood (? [95%CI]?=?0.22 [0.01,0.42], p?=?0.04; 0.11 [0.01,0.22], p?=?0.04), while infants born in the summer had higher Sb, logB, logHg, and logZn (? [95%CI]?=?0.74 [0.24,1.24], p?=?0.004; 0.11 [0.00,0.21], p?=?0.04; 0.29 [0.08,0.49], p?=?0.007; 0.18 [0.06,0.31], p?=?0.005), compared to those born in fall/winter. Prenatal heavy metal exposure and/or trace metal deficiencies are global concerns because of increasing awareness of downstream developmental effects.
| S-EPMC6179361 | biostudies-literature
Project description:OBJECTIVE:Damage to locus ceruleus neurons could play a part in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis because of impairment of the blood-brain barrier and enhanced neuroinflammation. The locus ceruleus has connections throughout the brain and spinal cord, so the characteristic widespread multifocal pathology in these disorders could be due to damage to different subsets of locus ceruleus neurons. Previous studies have shown that only certain locus ceruleus neurons accumulate the neurotoxic metal mercury. To find out if concentrations of other toxic metals or of essential trace elements also vary between individual locus ceruleus neurons, we used synchrotron X-ray fluorescence microscopy on frozen sections of locus ceruleus neurons taken from people with multiple sclerosis, in whom the locus ceruleus is structurally intact. MATERIALS AND METHODS:Paraffin embedded sections containing the locus ceruleus from seven people with multiple sclerosis were stained with autometallography that demonstrates accumulations of mercury, silver and bismuth. These were compared to maps of multiple elements obtained from frozen sections of locus ceruleus neurons from the same people using X-ray fluorescence microscopy. Neurons in the anterior pons from three of these donors were used as internal controls. RESULTS:Autometallography staining was observed in scattered locus ceruleus neurons from three of the seven donors. X-ray fluorescence microscopy showed variations among individual locus ceruleus neurons in levels of mercury, selenium, iron, copper, lead, bromine, and rubidium. Variations between donors of locus ceruleus neuronal average levels of mercury, iron, copper, and bromine were also detected. Anterior pons neurons contained no mercury, had varied levels of iron, and had lower copper levels than locus ceruleus neurons. CONCLUSIONS:Individual human locus ceruleus neurons contain varying levels of toxic metals and essential trace elements. In contrast, most toxic metals are absent or at low levels in nearby anterior pons neurons. The locus ceruleus plays a role in numerous central nervous system functions, including maintaining the blood-brain-barrier and limiting neuroinflammation. Toxic metals, or alterations in essential trace metals within individual locus ceruleus neurons, could be one factor determining the non-random destruction of locus ceruleus neurons in normal aging and neurodegenerative diseases, and subsequently the sites of the widespread multifocal central nervous system pathology in these disorders.
| S-EPMC7237016 | biostudies-literature
Project description:Summary An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced pore, the permeability transition pore (PTP). The molecular details of PTP are incompletely understood. We utilized holographic and fluorescent microscopy to assess the contribution of ATP synthase and adenine nucleotide translocator (ANT) toward PTP. In cells lacking either ATP synthase or ANT, we observed CSA-sensitive membrane depolarization, but not high-conductance PTP. In wild-type cells, calcium-induced CSA-sensitive depolarization preceded opening of PTP, which occurred only after nearly complete mitochondrial membrane depolarization. We propose that both ATP synthase and ANT are required for high-conductance PTP but not depolarization, which presumably occurs through activation of the low-conductance PT, which has a molecular nature that is different from both complexes. Graphical abstract Highlights • Both ATP synthase and ANT are required for permeabilization, but not depolarization• CSA-dependent depolarization precedes mitochondrial permeabilization• CSA-dependent depolarization is not dependent on ANT or ATP synthase• Mitochondria disappear from holographic images upon membrane permeabilization Molecular biology; Cell biology; Functional aspects of cell biology.
| S-EPMC9647522 | biostudies-literature
Project description:Toxic heavy metals (THMs) are contaminants commonly found in the environment. Although a large number of studies have demonstrated their damage to the biological functions of the human being, their potential associations with the risk of developing schizophrenia remain controversial. In this study, we investigated the associations between four THMs (chromium (Cr), cadmium (Cd), lead (Pb) and arsenic (As)) in serum and the risk of schizophrenia. In total, 95 patients with schizophrenia (cases) and 95 normal subjects (controls) were recruited from Hebei Province, China. The serum concentrations of the 4 THMs were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). A higher concentration of Pb was found significantly associated with an elevated risk of schizophrenia (OR = 3.146; 95%CI: 1.238-7.994, p = 0.016), while significant association for the other three THMs were not observed. Besides, significant correlations were found between the metabolic biomarkers and the concentrations of Pb and As, respectively. In order to further characterize the association between these THMs and schizophrenia with greater statistical power, we conducted meta-analysis by including 538 cases and 1040 controls from the current study and 5 available datasets published from 2002 to 2018. Using a random-effect model, Cr was significantly associated with schizophrenia (SMD = 0.3246; 95%CI: 0.0166-0.6326, p < 0.01). Overall, this study suggested that higher levels of Pb and Cr may be one of the factors associated with an elevated risk of schizophrenia.
| S-EPMC6862006 | biostudies-literature
Project description:Construction of the bacterial flagellum in the cell exterior proceeds at its distal end by highly ordered self-assembly of many different component proteins, which are selectively exported through the central channel of the growing flagellum by the flagellar type III export apparatus. FliI is the ATPase of the export apparatus that drives the export process. Here we report the 2.4 A resolution crystal structure of FliI in the ADP-bound form. FliI consists of three domains, and the whole structure shows extensive similarities to the alpha and beta subunits of F0F1-ATPsynthase, a rotary motor that drives the chemical reaction of ATP synthesis. A hexamer model of FliI has been constructed based on the F1-ATPase structure composed of the alpha3beta3gamma subunits. Although the regions that differ in conformation between FliI and the F1-alpha/beta subunits are all located on the outer surface of the hexamer ring, the main chain structures at the subunit interface and those surrounding the central channel of the ring are well conserved. These results imply an evolutionary relation between the flagellum and F0F1-ATPsynthase and a similarity in the mechanism between FliI and F1-ATPase despite the apparently different functions of these proteins.
| S-EPMC1766411 | biostudies-literature