Item – Theses Canada

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OCLC number
653384362
Link(s) to full text
LAC copy
LAC copy
Author
Bowden, Kristin,1982-
Title
Regulation of ABCA1 protein turnover and cholesterol efflux by oxysterol binding protein (OSBP).
Degree
M. Sc. -- Dalhousie University, 2008
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2009]
Description
2 microfiches
Notes
Includes bibliographical references.
Abstract
Oxysterols are the primary targets for liver X receptor (LXR) nuclear receptors that activate genes involved in cholesterol efflux and elimination, such as the ATP-binding cassette transporter (ABCA1). We tested whether oxysterol binding protein (OSBP), that binds cholesterol and oxysterols, is involved in ABCA1 regulation. OSBP was knocked down by RNA interference (RNAi). OSBP depletion in J774A.1 macrophage cells or Chinese hamster ovary cells (CHO)-K1 cells treated with the LXR agonists 22(R)- and 25-hydroxycholesterol (22-OH and 25OH) increased ABCA1 protein expression and efflux of [3H]cholesterol to apoA1. Quantification of ABCA1 mRNA levels and LXR reporter gene activity revealed that OSBP was not involved in transcriptional regulation of ABCA1. Rather, depletion of OSBP by siRNA decreased ABCA1 protein turnover by 3-fold following cycloheximide treatment, and co-transfection of ABCA1 and OSBP plasmids in CHO cells reduced ABCA1 expression. These findings implicate OSBP as a potential negative regulator of ABCA1 protein stability.
ISBN
9780494391549
0494391545