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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Lipid+Res
2016 ; 57
(3
): 451-63
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Glucosylated cholesterol in mammalian cells and tissues: formation and
degradation by multiple cellular ?-glucosidases
#MMPMID26724485
Marques AR
; Mirzaian M
; Akiyama H
; Wisse P
; Ferraz MJ
; Gaspar P
; Ghauharali-van der Vlugt K
; Meijer R
; Giraldo P
; Alfonso P
; Irún P
; Dahl M
; Karlsson S
; Pavlova EV
; Cox TM
; Scheij S
; Verhoek M
; Ottenhoff R
; van Roomen CP
; Pannu NS
; van Eijk M
; Dekker N
; Boot RG
; Overkleeft HS
; Blommaart E
; Hirabayashi Y
; Aerts JM
J Lipid Res
2016[Mar]; 57
(3
): 451-63
PMID26724485
show ga
The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded.
Cells express two GlcCer-degrading ?-glucosidases, glucocerebrosidase (GBA) and
GBA2, located in and outside the lysosome, respectively. Here we demonstrate that
through transglucosylation both GBA and GBA2 are able to catalyze in vitro the
transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa.
Furthermore, the natural occurrence of 1-O-cholesteryl-?-D-glucopyranoside
(GlcChol) in mouse tissues and human plasma is demonstrated using LC-MS/MS and
(13)C6-labeled GlcChol as internal standard. In cells, the inhibition of GBA
increases GlcChol, whereas inhibition of GBA2 decreases glucosylated sterol.
Similarly, in GBA2-deficient mice, GlcChol is reduced. Depletion of GlcCer by
inhibition of GlcCer synthase decreases GlcChol in cells and likewise in plasma
of inhibitor-treated Gaucher disease patients. In tissues of mice with
Niemann-Pick type C disease, a condition characterized by intralysosomal
accumulation of cholesterol, marked elevations in GlcChol occur as well. When
lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is
formed via lysosomal GBA. This illustrates that reversible transglucosylation
reactions are highly dependent on local availability of suitable acceptors. In
conclusion, mammalian tissues contain GlcChol formed by transglucosylation
through ?-glucosidases using GlcCer as donor. Our findings reveal a novel
metabolic function for GlcCer.