ISSN:
1432-1912
Keywords:
Key words Cycloheterophyllin
;
Neutrophil (rat)
;
Superoxide anion
;
Protein kinase C
;
Inositol trisphosphate
;
Intracellular Ca2+ concentration
;
NADPH oxidase
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Cycloheterophyllin, a prenylflavone, inhibited the superoxide anion (O2 -)generation from formylmethionyl-leucyl-phenylalanine (fMLP)- and phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils in a concentration-dependent manner with IC50 values of 47.0 ± 5.0 and 1.7 ± 0.4 μM, respectively. Cycloheterophyllin had no effect on O2 .- generation in xanthine-xanthine oxidase system and during dihydroxyfumaric acid (DHF) autoxidation. Cycloheterophyllin exerted a concentration-dependent inhibition of neutrophil cytosolic protein kinase C (PKC) and rat brain PKC, but had no effect on porcine heart protein kinase A (PKA). Unlike staurosporine, cycloheterophyllin did not affect the trypsin-treated rat brain PKC. [3H]Phorbol 12,13-dibutyrate ([3H]PDB) binding to neutrophil cytosolic PKC was significantly suppressed by cycloheterophyllin. However, cycloheterophyllin had negligible effect on the PMA-induced membrane translocation of PKC-β and PKC-δ in neutrophils. Moreover, the fMLP-induced [Ca2+]i elevation and inositol trisphosphate (IP3) formation of neutrophils were not affected by cycloheterophyllin at concentrations which significantly suppressed the O2 .- generation. In cell-free system, addition of arachidonate (AA) into the mixture of cytosol and membrane fractions of the resting neutrophils to make NADPH oxidase assembly and activation. Cycloheterophyllin had no effect on O2 .- generation in AA-activated cell-free system. These results suggest that the suppression of PKC activity through the interaction with the regulatory region of PKC is involved in the inhibition by cycloheterophyllin of the O2 .- generation in rat neutrophils.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00004982
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