In vitro binding of [14C]2,5-hexanedione to rat neuronal cytoskeletal proteins.


Journal Article

2,5-Hexanedione (2,5-HD) induces central-peripheral axonpathy characterized by the accumulation of 10-nm neurofilaments proximal to the nodes of Ranvier and a Wallerian-type degeneration. It has been postulated that neurofilament crosslinking may be involved in the production of this axonopathy. A potential initiating event in this neurotoxic process may be the direct binding of 2,5-HD to neurofilament and microtubule proteins. In this study, the in vitro binding of [14C]2,5-HD to neurofilament and microtubule proteins was examined. Neurofilament proteins isolated from rat spinal cord or microtubule proteins isolated from rat brain were incubated in the presence of 2,5-HD at concentrations ranging from 25 to 500 mM. Quantitative analysis of sodium dodecyl sulfate (SDS) polyacrylamide gels revealed a dose- and time-dependent binding of 2,5-HD to both neurofilament proteins and microtubule proteins. Expressed as pmol 2,5-HD bound per microgram protein, the observed relative binding was MAP2 > NF160 > NF200 > > NF68 > tubulin. These data demonstrate the direct binding of 2,5-HD to cytoskeletal proteins including both neurofilaments and microtubules.

Full Text

Duke Authors

Cited Authors

  • Lanning, CL; Wilmarth, KR; Abou-Donia, MB

Published Date

  • September 1, 1994

Published In

Volume / Issue

  • 19 / 9

Start / End Page

  • 1165 - 1173

PubMed ID

  • 7824070

Pubmed Central ID

  • 7824070

International Standard Serial Number (ISSN)

  • 0364-3190

Digital Object Identifier (DOI)

  • 10.1007/bf00965151


  • eng

Conference Location

  • United States