Comparative study of modification and degradation of neurofilament proteins in rats subchronically treated with allyl chloride, acrylamide, or 2,5-hexanedione.
Allyl chloride (ALL), acrylamide (ACR), and 2,5-hexanedione (2,5-HD) are all industrial neurotoxicants and known to produce accumulation of neurofilament (NF) proteins in both the central and peripheral nervous systems. To clarify whether any common mechanisms underlie these neurofilamentous axonopathies, the ability of ALL, ACR, and 2,5-HD to cross-link the NFs and the effects on NF degradation by Ca(2+)-activated neural protease were investigated in spinal cords from rats subchronically treated with these chemicals. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis revealed the appearance of high-molecular-weight species of NF triplets immunoreactive to each anti-68K, anti-160K, and anti-200K NF antibody in the 2,5-HD-treated rats, whereas it was not found in those treated with ALL or ACR. A time course study on the degradation of NF proteins conducted by the co-incubation with Ca2+ showed degradation resistance in all three NF subunits from animals treated with 2,5-HD, while no significant alterations in the rate of NF degradation were observed in the ALL- or ACR-treated group. The present results suggest that neurofilament-filled axonopathy induced by ALL or ACR and axonopathy induced by 2,5-HD may not share a common mechanism, though the initial step for the pathogenesis of this chemically induced neurotoxicity is not fully understood at present.
Nagano
M
M
Department of Public Health, Kumamoto University Medical School, Japan.
Yamamoto
H
H
Harada
K
K
Miyamoto
E
E
Futatsuka
M
M
D020106:Acrylamide; D000178:Acrylamides / Q000008:administration & dosage / Q000633:toxicity*; D000498:Allyl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006588:Hexanones / Q000008:administration & dosage / Q000633:toxicity*; D007271:Injections, Intradermal; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D016900:Neurofilament Proteins / Q000032:analysis / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D013116:Spinal Cord / Q000737:chemistry* / Q000187:drug effects; D013997:Time Factors
D000178:Acrylamides; D000498:Allyl Compounds; D006588:Hexanones; D016900:Neurofilament Proteins; D020106:Acrylamide; C011269:2,5-hexanedione; C023698:allyl chloride