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Papers In Press, published online ahead of print June 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500011-JLR200

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Journal of Lipid Research, Vol. 46, 1213-1228, June 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

ESI-MS quantitation of increased sphingomyelin in Niemann-Pick disease type B HDL

Ching Yin Lee^*, Alain Lesimple, Åsmund Larsen, Orval Mamer and Jacques Genest^1,*

^* Cardiovascular Genetics Laboratory, McGill University, Montréal, Canada
Department of Medicine, and Mass Spectrometry Unit, McGill University, Montréal, Canada
Department of Chemistry, University of Oslo, Oslo, Norway

The online version of this article (available at http://www.jlr.org) contains an additional figure and two tables.

Published, JLR Papers in Press, March 1, 2005. DOI 10.1194/jlr.M500011-JLR200

¹ To whom correspondence should be addressed. e-mail: jacques.genest{at}muhc.mcgill.ca

HDLs have been proposed to have antiatherogenic properties because of their role in reverse cholesterol transport as lipid acceptors. To elucidate the phospholipid profile of these particles, we used electrospray ionization mass spectrometry to examine the phosphatidylcholine (PC) and sphingomyelin (SM) composition of HDLs purified from plasma and nascently generated in vitro from fibroblasts. We also quantitatively compared the phospholipids present in these lipoproteins between normal and Niemann-Pick disease type B (NPD-B) subjects characterized by sphingomyelinase (SMase) deficiency. We demonstrated that plasma HDLs from NPD-B were significantly enriched in SM by an average of 28%, particularly the palmitoyl SM (with an increase of 95%), which accounted for 25–44% of total SM molecular species. Similarly, we observed an increase of 63% in total SM levels in nascent HDLs prepared from NPD-B fibroblasts. Although PC levels in nascent HDLs were comparable between control and NPD-B cells, there was a 95% increase in total PC levels similar to that of SM in plasma HDLs extracted from NPD-B subjects.

These data provide insight into the structure of HDLs and identify potential new roles for SMase in lipoprotein metabolism.

Abbreviations: apoA-I, apolipoprotein A-I; CID, collision-induced decomposition; ESI-MS, electrospray ionization-mass spectrometry; HDL-C, high density lipoprotein-cholesterol; NPD-B, Niemann-Pick disease type B; PC, phosphatidylcholine; SM, sphingomyelin; SMase, sphingomyelinase; SMPD-1, sphingomyelin phosphodiesterase-1

Supplementary key words electrospray ionization-mass spectrometry • phospholipids • sphingomyelin phosphodiesterase-1 gene • sphingomyelinase • high density lipoprotein

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