Lipoprotein lipase affects the survival and differentiation of neural cells exposed to very low density lipoprotein.
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 microm 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 CuSO(4), 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 CuSO(4) 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.
Paradis
Eric
E
Department of Medical Biology, Faculty of Medicine and Lipid Research Centre, Laval University Medical Research Centre, Laval University, Ste-Foy, Quebec G1K 7P4, Canada.
Clement
Sébastien
S
Julien
Pierre
P
Ven Murthy
M R
MR
D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D019327:Copper Sulfate / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors; D014162:Transfection
D018076:DNA, Complementary; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D017392:Thiobarbituric Acid Reactive Substances; D008071:Lipoprotein Lipase; D019327:Copper Sulfate; D010100:Oxygen