Compared effects of cholesterol and 7-dehydrocholesterol on sphingomyelin-glycerophospholipid bilayers studied by ESR.
The ESR of 7- and 16-doxylstearic spin-labeled fatty acids (7NS and 16NS, respectively) reveal the distinct influence of cholesterol or cholesterol precursor analogue, delta7-dehydrocholesterol, on the molecular ordering and the fluidity of lipid mixtures containing sphingomyelin (SM). The phase-separation of sphingomyelin domains mixed within fluid glycerophospholipids (phosphatidylethanolamine and phosphatidylserine) can be followed by ESR as a function of the temperature and in the presence of sterols [cholesterol (CHOL) or 7-dehydrocholesterol (DHCHOL)]. The time scale of spin-label exchange among phases is appropriate to follow the occurrence of the specific sphingomyelin/sterol association forming liquid ordered (Lo) microdomains which separate from the fluid surrounding phase Lalpha. Sphingomyelin embedded within the fluid bilayer associates with both sterols below 36 degrees C to give a phase Lo traceable by ESR in the form of a highly anisotropic component. Above 36 degrees C, the contribution in the ESR spectrum, of the Lo phase formed by 7-dehydrocholesterol with sphingomyelin is reduced by contrast with cholesterol forming a temperature-stable liquid ordered phase up to 42 degrees C. The consequences of this destabilization of the SM/sterol microdomains are envisioned in the biosynthesis defect where the precursor 7-dehydrocholesterol substitutes, for a significant part, the embryonic cell cholesterol.
Wolf
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Service de Biochimie, Laboratoire Commun de Spectrométrie, INSERM U538, Faculté de Médecine de Saint-Antoine, Paris, France. wolf@ccr.jussieu.fr
Chachaty
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D000818:Animals; D016880:Anisotropy; D002784:Cholesterol / Q000494:pharmacology*; D003497:Cyclic N-Oxides; D003684:Dehydrocholesterols / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D020404:Glycerophospholipids / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism*; D013113:Spin Labels; D013696:Temperature; D014961:X-Ray Diffraction
D003497:Cyclic N-Oxides; D003684:Dehydrocholesterols; D020404:Glycerophospholipids; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D013109:Sphingomyelins; D013113:Spin Labels; C055536:7-doxylstearic acid; C032363:16-nitroxystearic acid; D002784:Cholesterol; C016705:7-dehydrocholesterol