A possible mechanism of action of the neurotoxic agent iminodipropionitrile (IDPN): a selective aggregation of the medium and heavy neurofilament polypeptides (NF-M and NF-H)
Juvenile male rats treated acutely with the neurotoxic agent, iminodipropionitrile showed no changes in the levels of total neurofilament subunit mRNA or protein for up to 28 days. However, the drug promoted aggregation of the neurofilaments, both spontaneously upon isolation and in an in vitro reassembly assay. This observation correlated with a basic pI shift of the heavy neurofilament subunit, due to a yet to be identified modification. Because of the crucial involvement of this neurofilament subunit in axonal integrity, it is likely that iminodipropionitrile produces a major portion of its neurotoxicity through this mechanism.
Anderson
J P
JP
Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY 10029.
Carroll
Z
Z
Smulowitz
M
M
Lieberburg
I
I
D000818:Animals; D007381:Intermediate Filament Proteins / Q000187:drug effects*; D008297:Male; D009420:Nervous System / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007381:Intermediate Filament Proteins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile