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Biochemical evidence for lead and mercury induced transbilayer movement of phospholipids mediated by human phospholipid scramblase 1
Published in American Chemical Society
2013
PMID: 23659204
Volume: 26
   
Issue: 6
Pages: 918 - 925
Abstract
Human phospholipid scramblase 1(hPLSCR1) is a transmembrane protein involved in bidirectional scrambling of plasma membrane phospholipids during cell activation, blood coagulation, and apoptosis in response to elevated intracellular Ca2+ levels. Pb2+ and Hg2+ are known to cause procoagulant activation via phosphatidylserine exposure to the external surface in erythrocytes, resulting in blood coagulation. To explore its role in lead and mercury poisoning, hPLSCR1 was overexpressed in Escherichia coli BL21 (DE3) and purified using affinity chromatography. The biochemical assay showed rapid scrambling of phospholipids in the presence of Hg 2+ and Pb2+. The binding constant (Ka) was calculated and found to be 250 nM-1 and 170 nM-1 for Hg2+ and Pb2+, respectively. The intrinsic tryptophan fluorescence and far ultraviolet circular dichroism studies revealed that Hg2+ and Pb2+ bind to hPLSCR1 and induce conformational changes. hPLSCR1 treated with protein modifying reagent N-ethylmaleimide before functional reconstitution showed 40% and 24% inhibition in the presence of Hg2+ and Pb2+, respectively. This is the first biochemical evidence to prove the above hypothesis that hPLSCR1 is activated in heavy metal poisoning, which leads to bidirectional transbilayer movement of phospholipids. © 2013 American Chemical Society.
About the journal
JournalData powered by TypesetChemical Research in Toxicology
PublisherData powered by TypesetAmerican Chemical Society
ISSN0893228X
Open AccessNo
Concepts (34)
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    Lead
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    Membrane protein
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    Mercury
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    N ETHYLMALEIMIDE
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    Phospholipid
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    PHOSPHOLIPID SCRAMBLASE 1
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    Unclassified drug
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    Lipid bilayer
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    PHOSPHOLIPID TRANSFER PROTEIN
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    PLSCR1 PROTEIN, HUMAN
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    AFFINITY CHROMATOGRAPHY
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    Article
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    Circular dichroism
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    Conformational transition
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    Controlled study
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    Escherichia coli
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    Fluorescence analysis
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    LEAD POISONING
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    MERCURIALISM
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    Metal binding
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    Phospholipid bilayer
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    Protein conformation
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    Protein expression
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    Protein modification
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    Protein purification
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    Chemistry
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    Genetics
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    Human
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    Isolation and purification
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    Metabolism
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    Humans
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    Lipid bilayers
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    PHOSPHOLIPID TRANSFER PROTEINS
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    Phospholipids