PMID- 2562540
OWN - NLM
STAT- MEDLINE
DCOM- 19900628
LR  - 20161123
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 10
IP  - 4
DP  - 1989 Winter
TI  - Neurofilament protein crosslinking in gamma-diketone neuropathy: in vitro and in 
      vivo studies using the seaworm myxicola infundibulum.
PG  - 743-56
AB  - Neurofilament (NF) protein crosslinking has been proposed as the ultimate 
      pathogenetic mechanism underlying the neuropathies caused by the gamma-diketones 
      2,5-hexanedione (HD) and 3,4-dimethyl-2,5-hexanedione (DMHD). Mammalian models 
      have been used to investigate this hypothesis, but alternative experimental 
      models are needed. Myxicola infundibulum is a marine worm which is gaining 
      popularity in neuroscience research because of its large syncytial axon. A model 
      system using Myxicola has been developed to investigate NF crosslinking in worms 
      exposed to neurotoxic agents whose putative mechanisms involve covalent 
      crosslinking of NF proteins. In vitro studies using purified NF demonstrate that 
      progressive alkylation of Myxicola NF with [2,5-14C]DMHD is accompanied by NF 
      protein crosslinking. Rabbit anti-Myxicola NF antisera showed highly restricted 
      activity for Myxicola axoplasm and NF and were employed for immunoblotting 
      axoplasm from Myxicola treated in vivo with DMHD. A dramatic increase in high 
      molecular weight material was demonstrated in the axoplasm of treated worms, as 
      demonstrated by polyacrylamide gel electrophoresis, and the new high molecular 
      weight bands stained with the anti-NF antisera, indicating the presence of 
      anti-NF reactive material in the crosslinked protein. Further, there was 
      progression of crosslinking after cessation of exposure in vivo, an observation 
      which suggests oxidation of remaining pyrrolyl derivatives. These studies support 
      previous observations which suggest that NF crosslinking is the molecular event 
      which initiates NF aggregation in gamma-diketone neurotoxicity, and establish 
      Myxicola infundibulum as a useful species in which to study certain neurotoxic 
      compounds.
FAU - St Clair, M B
AU  - St Clair MB
AD  - Department of Pathology, Duke University Medical Center, Durham, North Carolina.
FAU - Anthony, D C
AU  - Anthony DC
FAU - Wikstrand, C J
AU  - Wikstrand CJ
FAU - Graham, D G
AU  - Graham DG
LA  - eng
GR  - ES02611/ES/NIEHS NIH HHS/United States
GR  - ES07031/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Hexanones)
RN  - 0 (Ketones)
RN  - 0 (Nerve Tissue Proteins)
RN  - 25234-79-1 (3,4-dimethyl-2,5-hexanedione)
RN  - C0Z8884J3P (2,5-hexanedione)
SB  - IM
MH  - Alkylation
MH  - Animals
MH  - Axons/metabolism/ultrastructure
MH  - Cross-Linking Reagents/metabolism
MH  - Cytoskeleton/*metabolism
MH  - Hexanones/*toxicity
MH  - Immunohistochemistry
MH  - Intermediate Filaments/*metabolism
MH  - Ketones/*toxicity
MH  - Nerve Tissue Proteins/*metabolism
MH  - Nervous System Diseases/chemically induced/*metabolism
MH  - Polychaeta
EDAT- 1989/01/01 00:00
MHDA- 1989/01/01 00:01
CRDT- 1989/01/01 00:00
PHST- 1989/01/01 00:00 [pubmed]
PHST- 1989/01/01 00:01 [medline]
PHST- 1989/01/01 00:00 [entrez]
PST - ppublish
SO  - Neurotoxicology. 1989 Winter;10(4):743-56.