Phospholipid matrix as a target for sulfur mustard (HD): NMR study in model membrane systems

• Published in: Cell biology and toxicology Vol. 18; no. 6; pp. 397 - 408
• Main Authors: DEBOUZY, J. C, AOUS, S, DABOUIS, V, NEVEUX, Y, GENTILHOMME, E
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.01.2002; Springer Nature B.V
• Subjects: Bilayers; Biological and medical sciences; Chains; Chemical and industrial products toxicology. Toxic occupational diseases; Dimyristoylphosphatidylcholine; Dimyristoylphosphatidylcholine - chemistry; Dose-Response Relationship, Drug; Fluidity; Gas, fumes; Intoxication; Lecithin; Lipid Bilayers - chemistry; Localization; Magnetic Resonance Spectroscopy; Medical sciences; Membrane fluidity; Membrane Fluidity - drug effects; Membranes; Models, Chemical; Multilayers; Mustard gas; Mustard Gas - chemistry; NMR; Nuclear magnetic resonance; Nucleic acids; Phosphatidic Acids - chemistry; Phosphatidylcholines - chemistry; Phospholipids; Phospholipids - chemistry; Pore formation; Sulfur; Toxicology; Transition temperature; Transition temperatures; Vesicles; yperite; Multilayer; Toxicity; Sulfur mustard; Phospholipid; NMR spectrometry; Large unilamellar vesicle; In vitro; membrane interactions; Gases; Lamellar structure; NMR; Membrane transport; Plasma membrane; Mechanism of action; Small unilamellar vesicle; model membranes
• ISSN: 0742-2091; 1573-6822
• DOI: 10.1023/A:1020815723009

Although the interactions of sulfur mustard (HD) with nucleic acids and proteins have been well studied, the toxic interactions with the membrane matrix and specially the phospholipid bilayer have so far been poorly investigated. We have used several NMR techniques to study these interactions: 1H NMR to observe the localization of HD in membranes of small unilamellar vesicles (SUV) of lecithin; 31P NMR to verify the hypothesis of pore formation in membranes of large unilamellar vesicles (LUV); and pseudo solid state 31P and 2H NMR to analyze the dynamic consequences of the presence of HD in multilayer dispersions of dimyristoylphosphatidylcholine (DMPC). Immediate and late modifications of the DMPC-HD complexes have been observed at the macroscopic and microscopic levels. After intoxication, HD is spontaneously incorporated into the membrane and locates at the level of the chain methylene groups. This incorporation occurs without formation of pores in the membrane. The presence of HD in the phospholipid dispersion differentially increases the membrane fluidity depending upon the level involved. Weak at the superficial level (phosphate group), this increase is dose-dependent on progression into the membrane. This increase is related to a lowering of transition temperature when measured at the chain level. Macroscopically, HD induces dose- and time-dependent modifications of the DMPC-HD complexes, leading to the formation of an optically transparent gel. This gel formation is confirmed at a microscopic level, where all structures disappear after intoxication.