Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells.
Nerve trauma initiates significant changes in the composition of proteins secreted by nonneuronal cells. The most prominent of these proteins is a 37-kDa protein, whose expression correlates with the time course of nerve development, degeneration, and regeneration. We now report that the 37-kDa protein is apolipoprotein E (apoE). We produced a specific antiserum against the 37-kDa protein isolated from previously crushed nerves. This antiserum recognizes a 36-kDa protein in rat serum that we have purified and identified as apoE. The anti-37-kDa antiserum also recognizes apoE on electrophoretic transfer blots of authentic samples of high and very low density lipoproteins. The nerve 37-kDa protein comigrates with apoE by two-dimensional electrophoresis, shares a similar amino acid composition, and reacts with an antiserum against authentic apoE. The purified apoE specifically blocks the immunoprecipitation of [35S]methionine-labeled 37-kDa protein synthesized by nonneuronal cells. Thus, on the basis of its molecular mass, isoelectric point, amino acid composition, and immunological properties, we conclude that the 37-kDa protein is apoE. We also used light microscopic immunohistochemistry to localize apoE following nerve injury. In rats with optic nerve lesions, the 37-kDa antiserum bound specifically to the degenerating optic tracts and to the retino-recipient layers of the lateral geniculate nucleus and the superior colliculus. We propose that apoE is synthesized by phagocytic cells in response to nerve injury for the purpose of mobilizing lipids produced as a consequence of axon degeneration.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001057:Apolipoproteins E / Q000276:immunology / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D009409:Nerve Crush; D009410:Nerve Degeneration; D009416:Nerve Regeneration; D020221:Optic Nerve Injuries; D010586:Phagocytes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries
D000596:Amino Acids; D001057:Apolipoproteins E