PAF analogues capable of inhibiting PAF acetylhydrolase activity suppress migration of isolated rat cerebellar granule cells

Tomoya Adachi, Junken Aoki, Hiroshi Manya, Hiroaki Asou, Hiroyuki Arai, Keizo Inoue

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Intracellular platelet-activating factor (PAF) acetylhydrolase in the bovine brain is a heterotrimeric enzyme composed of α1, α2 and β subunits. The trimeric enzyme may be involved in neural cell migration, since the human homolog of the non-catalytic β subunit is a product of the LIS-1 gene which is a causative gene for Miller-Dieker syndrome. Miller-Dieker syndrome is a form of lissencephaly that is characterized by widespread agyria of the brain and defects of neuronal cell migration. In the present study, we attempted to determine whether the catalytic activity of either the α1 or α2 subunit is required for the regulation of granule cell migration. Granule cells prepared from rat cerebellum at postnatal day 0 express all three subunit proteins (α1, a2 and β) as determined by western blotting. Granule cell migration, which was observed in vitro on a layer coated with laminin, was effectively blocked by PAF analogs which showed PAF receptor-antagonistic activity (CV- 6209 and CV-3988) and PAF receptor-agonistic activity (carbamoyl PAF). These PAF analogs also inhibited the activity of bovine brain PAF acetylhydrolase. Cell migration was restored when the inhibitors were removed by washing the treated cells with buffer, indicating that the inhibitory effect of PAF analogs is reversible. Structurally-unrelated PAF antagonists (SM-12502, TCV- 309 and YM-264), none of which showed any appreciable inhibitory activity against PAF acetylhydrolase, did not block granule cell migration under the same conditions. It is suggested that the catalytic activity of PAF acetylhydrolase may play a crucial role in neural cell migration.

Original languageEnglish
Pages (from-to)133-136
Number of pages4
JournalNeuroscience Letters
Volume235
Issue number3
DOIs
Publication statusPublished - 1997 Oct 17
Externally publishedYes

Keywords

  • Granule cell
  • Miller-Dieker syndrome
  • Neural cell migration
  • Platelet-activating factor
  • Platelet-activating factor acetylhydrolase

ASJC Scopus subject areas

  • Neuroscience(all)

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