The role of pyrrole formation in the alteration of neurofilament transport induced during exposure to 2,5-hexanedione.
Exposure to the gamma-diketone, 2,5-hexanedione (HD), results in the accumulation of neurofilaments within the distal axon and is associated with acceleration of neurofilament transport within the proximal axon. The epsilon-amino groups of lysyl residues react with HD forming pyrrole adducts, followed by pyrrole-mediated protein crosslinking. Both reaction steps have been proposed as mechanisms causing neurofilament accumulation and acceleration of transport. In order to assess the importance of these steps on neurofilament transport, we compared transport in the optic system of rats exposed to HD and 3-acetyl-2,5-hexanedione (AcHD), a non-toxic analog of HD which forms pyrroles but does not crosslink proteins. Control, HD-treated, and AcHD-treated rats received intraoptic injections of [35S]-methionine and were exposed to saline, HD, or AcHD by intraperitoneal injections before and during the period of neurofilament transport. Neurofilament triplet proteins in the optic nerve and tract were identified by polyacrylamide gel electrophoresis followed by fluorography. The rate of neurofilament transport was accelerated in HD-treated animals over that of controls. However, despite higher levels of protein-bound pyrroles in AcHD-treated animals, the rate of transport was indistinguishable from that of controls. These findings indicate that pyrrole formation alone is not sufficient to cause acceleration of neurofilament transport.
Pyle
S J
SJ
Duke University Medical Center, Durham, North Carolina 27710.
Amarnath
V
V
Graham
D G
DG
Anthony
D C
DC
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006588:Hexanones / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism*; D011758:Pyrroles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006588:Hexanones; D016900:Neurofilament Proteins; D011758:Pyrroles; C011269:2,5-hexanedione