Acrylamide and carbon disulfide treatments increase the rate of rat brain tubulin polymerization.
Acrylamide and carbon disulfide produce central-peripheral distal axonopathy in experimental animals and humans. The main feature of this disease is the focal swellings containing neurofilaments in distal axons, followed by nerve degeneration beyond these swellings. We studied the possible role of tubulin assembly kinetics in this disease. The rats were either administered acrylamide (50 mg/kg, ip, saline) or exposed to carbon disulfide (700 ppm, 9 h) via inhalation for 12 and 15 d, respectively. Tubulin, purified from both acrylamide-(10.37 +/- 0.3 vs 11.3 +/- 0.15) and carbon disulfide-treated (9.72 +/- 0.5 vs 11.18 +/- 0.25) rat brains showed increase in Vmax (OD/min x 10(3)) of its polymerization. However, only acrylamide treatment showed a decrease in time to Vmax, when brain supernatant was used for tubulin polymerization. In vitro addition of acrylamide (0.1-1 mM) to bovine brain tubulin also showed a decrease in time to Vmax (16-21%) of its polymerization. Carbon disulfide treatment of rats, on the other hand, showed a decrease in MAP-2 and an increase in a 120-kDa peptide concentration. The latter showed immunoreactivity with anti-MAP-2. The increase in the rate of tubulin polymerization by acrylamide and carbon disulfide treatment may alter the rate of transport of axonal constituents, including neurofilament, and contribute toward their accumulation in the focal swellings observed in this neuropathy.
Gupta
R P
RP
Duke University Medical Center, Department of Pharmacology, Durham, NC 27708, USA.
Abou-Donia
M B
MB
D000178:Acrylamides / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002246:Carbon Disulfide / Q000494:pharmacology*; D002417:Cattle; D002675:Child, Preschool; D006224:Cricetinae; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism*
D000178:Acrylamides; D008869:Microtubule-Associated Proteins; D011108:Polymers; D014404:Tubulin; D002246:Carbon Disulfide