Acrylamide-regulated neurofilament expression in rat pheochromocytoma cells.

Published

Journal Article

Using the rat pheochromocytoma cell line (PC12), we present molecular evidence that the neurotoxicant acrylamide directly induces neurofilament gene expression, and the signaling pathways are initially distinctive from, but eventually merged into, that for nerve growth factor (NGF)-induced neurofilament expression. In PC12 cells, acrylamide increased neurofilament protein levels and synthesis. Acrylamide had no effect on the stability of neurofilament mRNAs suggesting that it directly increased neurofilament mRNA synthesis. K252a, a selective inhibitor for NGF receptor gp140trk, had no effect on acrylamide induction, but completely inhibited NGF-induced neurofilament protein synthesis. Therefore, the initial step for acrylamide signaling was distinctive from NGF. Dexamethasone reversed the effects of both NGF and acrylamide on neurofilament protein levels and synthesis indicated that there is a dexamethasone-sensitive signaling step upon which NGF and acrylamide merge, suggesting involvement of transcription-activating proteins like AP-1. These results, taken together with previous studies of transgenic mice that overexpress neurofilament genes, may partially explain the mechanisms of neurofilament accumulation in distal parts of large axons, a pathognomonic feature of acrylamide neurotoxicity in animals.

Full Text

Duke Authors

Cited Authors

  • Lin, WW; Friedman, MA; Wang, XF; Abou-Donia, MB

Published Date

  • January 10, 2000

Published In

Volume / Issue

  • 852 / 2

Start / End Page

  • 297 - 304

PubMed ID

  • 10678756

Pubmed Central ID

  • 10678756

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/s0006-8993(99)02104-6

Language

  • eng

Conference Location

  • Netherlands