Abstract
Lipoproteins originating from axon and myelin breakdown in injured peripheral nerves are believed to supply cholesterol to regenerating axons. We have used compartmented cultures of rat sympathetic neurons to investigate the utilization of lipids from lipoproteins for axon elongation. Lipids and proteins from human low density lipoproteins (LDL) and high density lipoproteins (HDL) were taken up by distal axons and transported to cell bodies, whereas cell bodies/proximal axons internalized these components from only LDL, not HDL. Consistent with these observations, the impairment of axonal growth, induced by inhibition of cholesterol synthesis, was reversed when LDL or HDL were added to distal axons or when LDL, but not HDL, were added to cell bodies. LDL receptors (LDLRs) and LR7/8B (apoER2) were present in cell bodies/proximal axons and distal axons, with LDLRs being more abundant in the former. Inhibition of cholesterol biosynthesis increased LDLR expression in cell bodies/proximal axons but not distal axons. LR11 (SorLA) was restricted to cell bodies/proximal axons and was undetectable in distal axons. Neither the LDL receptor-related protein nor the HDL receptor, SR-B1, was detected in sympathetic neurons. These studies demonstrate for the first time that lipids are taken up from lipoproteins by sympathetic neurons for use in axonal regeneration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Anticholesteremic Agents / pharmacology
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Axons / metabolism
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Axons / physiology*
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Brain / metabolism
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CD36 Antigens / biosynthesis
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Cell Division
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Cells, Cultured
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Electrophoresis, Polyacrylamide Gel
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Humans
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Immunoblotting
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LDL-Receptor Related Proteins
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Lipoproteins / pharmacokinetics*
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Lipoproteins, HDL / pharmacokinetics
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Lipoproteins, LDL / pharmacokinetics
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Liver / metabolism
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Low Density Lipoprotein Receptor-Related Protein-1
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Membrane Proteins*
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Membrane Transport Proteins*
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Microscopy, Fluorescence
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Models, Biological
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Neurons / cytology*
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Neurons / metabolism
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Pravastatin / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Immunologic / biosynthesis
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Receptors, LDL / biosynthesis
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Receptors, Lipoprotein / biosynthesis
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Receptors, Scavenger
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Scavenger Receptors, Class B
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Sympathetic Nervous System / metabolism*
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Tissue Distribution
Substances
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Anticholesteremic Agents
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CD36 Antigens
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LDL-Receptor Related Proteins
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Lipoproteins
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Lipoproteins, HDL
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Lipoproteins, LDL
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Low Density Lipoprotein Receptor-Related Protein-1
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Membrane Proteins
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Membrane Transport Proteins
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Receptors, Immunologic
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Receptors, LDL
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Receptors, Lipoprotein
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Receptors, Scavenger
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SCARB1 protein, human
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SORL1 protein, human
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Scarb1 protein, mouse
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Scarb1 protein, rat
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Scavenger Receptors, Class B
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Sorl1 protein, mouse
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Sorl1 protein, rat
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low density lipoprotein receptor-related protein 8
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Pravastatin