PMID- 7658912
OWN - NLM
STAT- MEDLINE
DCOM- 19951002
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 57
IP  - 11
DP  - 1995
TI  - PGI2 analogue, sodium beraprost, suppresses superoxide generation in human 
      neutrophils by inhibiting p47phox phosphorylation.
PG  - 1051-9
AB  - Sodium beraprost, a newly synthesized PGI2 analogue inhibited in a dose-dependent 
      manner formyl-methionyl-leucyl-phenylalanine (fMLP) induced superoxide generation 
      of human neutrophils, but it had no effect on the superoxide synthesis by phorbol 
      myristate acetate (PMA) or A23187. Sodium beraprost inhibited Ca2+ influx in fMLP 
      stimulated neutrophils employing fluorometry and confocal microscopy. These 
      findings suggested that the inhibitory effect of sodium beraprost on fMLP induced 
      superoxide generation was due to suppression of Ca2+ influx. To examine the 
      relationship between the effect of sodium beraprost and phosphorylation of 
      p47phox (the 47kDa cytosolic phagocyte oxidase factor), immuno-precipitation of 
      p47phox and western blotting for phospho-amino acids were performed. 
      Phosphorylation of serine residues of p47phox induced by fMLP was reduced in the 
      presence of sodium beraprost in a dose-dependent manner. The reduction in 
      phosphorylation was accompanied by a reduction in p47phox and p67phox 
      translocation to the plasma membrane and superoxide generation. These findings 
      suggested that p47phox phosphorylation was necessary for translocation and 
      superoxide generation in fMLP activated neutrophils, and that p47phox 
      phosphorylation was regulated by a Ca2+ dependent mechanism. These observations 
      suggested that sodium beraprost inhibited fMLP induced superoxide generation of 
      human neutrophils by the inhibition of p47phox phosphorylation and translocation 
      by a Ca2+ dependent mechanism.
FAU - Okuyama, M
AU  - Okuyama M
AD  - Department of Surgery II, Osaka University Medical School, Japan.
FAU - Kambayashi, J
AU  - Kambayashi J
FAU - Sakon, M
AU  - Sakon M
FAU - Kawasaki, T
AU  - Kawasaki T
FAU - Monden, M
AU  - Monden M
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Phosphoproteins)
RN  - 11062-77-4 (Superoxides)
RN  - 35E3NJJ4O6 (beraprost)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
RN  - EC 1.6.99.1 (NADPH Dehydrogenase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcimycin/pharmacology
MH  - Calcium/metabolism
MH  - Epoprostenol/*analogs & derivatives/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - NADPH Dehydrogenase/*metabolism
MH  - NADPH Oxidases
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Respiratory Burst/*drug effects
MH  - Superoxides/*metabolism
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 002432059502050S [pii]
AID - 10.1016/0024-3205(95)02050-s [doi]
PST - ppublish
SO  - Life Sci. 1995;57(11):1051-9. doi: 10.1016/0024-3205(95)02050-s.