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Originally published In Press as doi:10.1074/jbc.M208452200 on December 24, 2002
J. Biol. Chem., Vol. 278, Issue 11, 9698-9705, March 14, 2003
Lipoprotein Lipase Affects the Survival and Differentiation of
Neural Cells Exposed to Very Low Density Lipoprotein*
Eric
Paradis ,
Sébastien
Clément ,
Pierre
Julien§, and
M. R.
Ven
Murthy ¶
From the Department of Medical Biology, Faculty of
Medicine and § Lipid Research Centre, Laval University
Medical Research Centre, Laval University, Ste-Foy,
Quebec G1K 7P4, Canada
Lipoprotein lipase (LPL) is a key enzyme involved
in the metabolism of lipoproteins, providing tissues like adipose
tissue or skeletal muscle with fatty acids. LPL is also expressed in the brain, fulfilling yet unknown functions. Using a neuroblastoma cell
line transfected with a NEO- or a LPL-expression vector, we have
developed a model to study the function of LPL in neurons exposed to
native or copper-oxidized lipoproteins. The addition to the culture
media of VLDL with 10 µM copper sulfate led to a
significant reduction in the viability of NEO transfectants whereas
LPL-transfectants were protected from this injury. In the presence of
VLDL and CuSO4, LPL transfectants were even able to display
significant neurite extension. This neuritogenic effect was also
observed in LPL transfectants exposed to native lipoproteins. However,
addition of VLDL particles oxidized with CuSO4 prior to
their addition to the culture media resulted in neurotoxic effects on
LPL transfectants. These findings suggest that the presence of LPL in
cultured neuronal cells modulates the physiological response of neurons
following exposure to native or oxidized lipoproteins. LPL could thus
play a key role in the differentiation of Neuro-2A cells and in the
pathophysiological effects of oxidative stress in several
neurodegenerative disorders.
*
This work was supported by a research grant from the
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
To whom correspondence should be addressed: Dept. of Medical
Biology, Faculty of Medicine, Laval University, Ste-Foy, Quebec G1K
7P4, Canada. Tel.: 418-656-3156; Fax: 418-656-7033; E-mail: Ven.
Murthy{at}bcx.ulaval.ca.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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