Cross-linking of neurofilament proteins of rat spinal cord in vivo after administration of 2,5-hexanedione.
Lapadula-DM; Irwin-RD; Suwita-E; Abou-Donia-MB
J Neurochem 1986 Jun; 46(6):1843-1850
Crosslinking of spinal cord neurofilament proteins induced by 2,5- hexanedione (110134) (25HD) was studied in rats. Male Sprague- Dawley-rats were administered 0.5% 25HD in their drinking water for 180 days. Rats were then killed and the spinal cords were removed. The neurofilament proteins were isolated and examined by sodium- dodecyl-sulfate polyacrylamide gel electrophoresis. 25HD caused significant decreases in the amounts of proteins having molecular weights of 70, 160, and 210 kilodaltons (kDa). Bands migrating at 58, 138, and 260kDa were also detected. These proteins were not found in control animals. The loss of the 70, 160, and 210kDa proteins and the appearance of new protein bands suggested that the 138 and 260kDa bands were formed as a result of crosslinking. The protein bands were examined by an immunoblotting technique using antibodies raised against the 70, 160, and 210kDa proteins. Significant immunoreactivity involving high molecular weight proteins was seen to the 70, 160, and 210kDa bands. The 138kDa protein reacted with the anti 160kDa antibody. A significant decrease in immunoreactive breakdown proteins, most evident with the 70kDa protein, was seen in the neurofilament protein preparations from the 25HD animals, but not the controls. The authors conclude that significant evidence for in-vivo crosslinking of neurofilament proteins in 25HD treated rats has been found. This suggests that protein crosslinking plays a role in 25HD induced neuropathy.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Spinal-cord; Ketones; In-vivo-studies; Laboratory-animals; Drinking-water; Nerve-fibers
Pharmacology Duke University Department of Pharmacology Durham, NC 27710
Journal of Neurochemistry
Duke University, Durham, North Carolina