Direct binding of sulfur mustard and chloroethyl ethyl sulphide to human cell membrane-associated proteins; implications for sulfur mustard pathology. 2010

N M Sayer, and R Whiting, and A C Green, and K Anderson, and J Jenner, and C D Lindsay
Biomedical Sciences, Defence Science and Technology Laboratory, Salisbury, Wiltshire SP4 OJQ, United Kingdom. nsayer@dstl.gov.uk

Sulfur mustard (SM) is a potent vesicating agent that produces debilitating blisters and ulcerating lesions on the skin which are characteristically slow to heal. There are currently no specific medical countermeasures to prevent SM-induced vesication and therefore SM remains a major military threat. To investigate the mechanism by which SM causes these injuries we aimed to identify the cellular proteins that are important in the vesicant response and pathology of SM. Membrane and membrane-associated proteins that are targets for direct binding by SM were compared to targets directly bound by CEES (chloroethylethylsulphide). As CEES is a less potent blistering agent compared to SM, it was hypothesised that differences in the binding of these two mustards could reveal key proteins directly involved in the mustard vesicant response. Human cellular membranes fractionated from HaCaT cells were exposed to (14)C-SM or (14)C-CEES and the membrane proteins to which SM or CEES bound were separated by 2D gel electrophoresis, located by fluorography and subsequently identified using mass spectrometry. A number of proteins were identified that were differentially labelled by SM and CEES. Actin, annexin A2 and keratin 9 were labelled with SM at a higher intensity than was seen with the same concentration of CEES. Therefore results from these studies suggest that SM binding to these proteins could contribute to the complex pathology seen following SM exposure.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D009151 Mustard Gas Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). Dichlorodiethyl Sulfide,Sulfur Mustard,Bis(beta-chloroethyl) Sulfide,Di-2-chloroethyl Sulfide,Mustardgas,Psoriazin,Yellow Cross Liquid,Yperite,Di 2 chloroethyl Sulfide,Gas, Mustard,Mustard, Sulfur,Sulfide, Di-2-chloroethyl,Sulfide, Dichlorodiethyl
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010449 Peptide Mapping Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases. Fingerprints, Peptide,Peptide Fingerprinting,Protein Fingerprinting,Fingerprints, Protein,Fingerprint, Peptide,Fingerprint, Protein,Fingerprinting, Peptide,Fingerprinting, Protein,Mapping, Peptide,Peptide Fingerprint,Peptide Fingerprints,Protein Fingerprint,Protein Fingerprints
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002247 Carbon Isotopes Stable carbon atoms that have the same atomic number as the element carbon but differ in atomic weight. C-13 is a stable carbon isotope. Carbon Isotope,Isotope, Carbon,Isotopes, Carbon
D002458 Cell Fractionation Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS. Cell Fractionations,Fractionation, Cell,Fractionations, Cell
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002619 Chemical Warfare Agents Chemicals that are used to cause the disturbance, disease, or death of humans during WARFARE. Agents, Chemical Warfare,Warfare Agents, Chemical,Agent, Chemical Warfare,Chemical Warfare Agent,Warfare Agent, Chemical
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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