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Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture.

ABSTRACT: Bromine is ubiquitously present in animals as ionic bromide (Br(-)) yet has no known essential function. Herein, we demonstrate that Br(-) is a required cofactor for peroxidasin-catalyzed formation of sulfilimine crosslinks, a posttranslational modification essential for tissue development and architecture found within the collagen IV scaffold of basement membranes (BMs). Bromide, converted to hypobromous acid, forms a bromosulfonium-ion intermediate that energetically selects for sulfilimine formation. Dietary Br deficiency is lethal in Drosophila, whereas Br replenishment restores viability, demonstrating its physiologic requirement. Importantly, Br-deficient flies phenocopy the developmental and BM defects observed in peroxidasin mutants and indicate a functional connection between Br(-), collagen IV, and peroxidasin. We establish that Br(-) is required for sulfilimine formation within collagen IV, an event critical for BM assembly and tissue development. Thus, bromine is an essential trace element for all animals, and its deficiency may be relevant to BM alterations observed in nutritional and smoking-related disease. PAPERFLICK:

SUBMITTER: McCall AS

PROVIDER: S-EPMC4144415 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture.

McCall A Scott AS Cummings Christopher F CF Bhave Gautam G Vanacore Roberto R Page-McCaw Andrea A Hudson Billy G BG

Cell 20140601 6

Bromine is ubiquitously present in animals as ionic bromide (Br(-)) yet has no known essential function. Herein, we demonstrate that Br(-) is a required cofactor for peroxidasin-catalyzed formation of sulfilimine crosslinks, a posttranslational modification essential for tissue development and architecture found within the collagen IV scaffold of basement membranes (BMs). Bromide, converted to hypobromous acid, forms a bromosulfonium-ion intermediate that energetically selects for sulfilimine fo ...[more]

PMID: 24906154

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Project description:Increasing illicit drug use is one of the main problems in most countries or societies. Monitoring heavy metals and trace elements in this vulnerable group seems to be necessary. Therefore, we assessed the urinary trace element and toxic metals/metalloids concentrations (Zinc (Zn), Iron (Fe), Copper (Cu), Chromium (Cr), Lead (Pb), Cadmium (Cd), Arsenic (As), Nickel (Ni), and Mercury (Hg)) in opium, tramadol, and cannabis users compared to healthy subjects. In this cross-sectional study, patients with substance use disorder (SUD) (n = 74) were divided into four groups: cannabis, tramadol, opium, and mixed (simultaneous use of more than one of the three studied substances), along with a healthy group (n = 60). Urine samples were prepared by dispersive liquid-liquid microextraction method so that heavy metals/metalloids could be measured by ICP-MS. The mean urinary concentration of Cu (48.15 vs. 25.45; 89.2%, p<0.001), Hg (1.3 vs. 0.10; 1200%, p < 0.001), and Zn (301.95 vs. 210; 43.8%, p < 0.001) was markedly lower among patients with SUD. The mean urinary concentration of other elements including As (1.9 vs. 4.1; 115.8%), Cd (0.1 vs. 1.10; 1000%), Cr (6.80 vs. 11.65; 71.3%), Ni (2.95 vs. 4.95; 67.8%), and Pb (1.5 vs. 7.9; 426.6%) were significantly higher among patients with SUD compared to healthy subjects. When sub-groups were compared, no significant differences were observed between their trace element levels (Kruskal-Wallis test, p > 0.05). This can be an indication that regardless of the type of drug, the levels of trace elements are changed with respect to healthy individuals. Our results showed that illicit drug use causes changes in urinary trace element/heavy metal/metalloid levels and highlights the need for monitoring heavy metals and trace elements in individuals with substance use disorder. Assessment of different elements in biological samples of drug dependents may be useful for implementing new prevention and treatment protocols. In case of changes in their levels, complementary recommendations, attention to diet, and periodic assessment of toxic metal levels within treatment programs will be needed.

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Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture.

Publications

Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture.

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