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 language | English |
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Pages (from-to) | 279-283 |
Number of pages | 5 |
Journal | Parasitology |
Volume | 114 |
Issue number | 3 |
Publication status | Published - Mar 1997 |
Keywords
- calcineurin
- parasites
- Hymenolepis spp.
- cyclosporin
- cyclophilin
- BINDING
- SUBUNIT
- FK506
- CYCLOPHILIN
- RAPAMYCIN
- PROTEINS
- DOMAIN
- cyclophilin