Characterization of calcineurin from Hymenolepis microstoma and H-diminuta and its interaction with cyclosporin A

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The drug cyclosporin A (CsA) exerts its immunosuppressive action by binding to the cytosolic protein, cyclophilin (CyP) and, as a complex, binding to and inhibiting the calcium/calmodulin-dependent serine threonine phosphatase, calcineurin. It is unknown whether a similar mode of action occurs during the drug's antiparasite activity. Calmodulin-binding proteins from the helminth parasites Hymenolepis microstoma and H. diminuta were purified by affinity chromatography, yielding single polypeptide bands of 60 000 M(r), according to SDS-PAGE. These proteins were tested for calcineurin activity by the dephosphorylation of the R(II) peptide (part of the catalytic subunit of cAMP-dependent protein kinase). Both proteins were calcium- and calmodulin-dependent and were inhibited by mammalian cyclophilin complexed with cyclosporin A (IC50 values of 0 . 75 mu g CyP for H. microstoma and 0 . 90 mu g CyP for H. diminuta). However, neither of the parasite calcineurins was inhibited by H. microstoma cyclophilin/CsA. These data suggest the anthelmintic mode of action of CsA in these helminth models does not involve the inhibition of a signal transduction pathway requiring interaction with calcineurin.

Original languageEnglish
Pages (from-to)279-283
Number of pages5
JournalParasitology
Volume114
Issue number3
Publication statusPublished - Mar 1997

Keywords

  • calcineurin
  • parasites
  • Hymenolepis spp.
  • cyclosporin
  • cyclophilin
  • BINDING
  • SUBUNIT
  • FK506
  • CYCLOPHILIN
  • RAPAMYCIN
  • PROTEINS
  • DOMAIN
  • cyclophilin

Cite this