PMID- 12928764
OWN - NLM
STAT- MEDLINE
DCOM- 20040806
LR  - 20211203
IS  - 0028-1298 (Print)
IS  - 0028-1298 (Linking)
VI  - 368
IP  - 3
DP  - 2003 Sep
TI  - The blockade of formyl peptide-induced respiratory burst by 
      2',5'-dihydroxy-2-furfurylchalcone involves phospholipase D signaling in 
      neutrophils.
PG  - 166-74
AB  - The inhibition of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced 
      respiratory burst by 2',5'-dihydroxy-2-furfurylchalcone (DHFC) was investigated 
      in rat neutrophils, and the underlying mechanism of this inhibition was assessed. 
      DHFC concentration-dependently inhibited superoxide anion (O(2)) generation 
      (IC(50) 4.2+/-1.2 microM), reaching a plateau within 5-10 min preincubation time, 
      and inhibited oxygen consumption (IC(50) 6.9+/-1.9 microM) in rat neutrophils. In 
      cell-free systems, DHFC failed to scavenge the generated during dihydroxyfumaric 
      acid auto-oxidation. DHFC was less effective in the inhibition of both phorbol 
      12-myristate 13-acetate-activated neutrophil particulate NADPH oxidase activity 
      and arachidonic acid-induced NADPH oxidase activation. In rat neutrophils, DHFC 
      did not exert a cAMP-elevating effect, nor did it affect fMLP-induced [Ca(2+)](i) 
      change to a considerable extent. DHFC slightly reduced fMLP-induced 
      phosphatidylinositol 3-kinase (PI3 K) activation but showed moderate inhibition 
      of Akt phosphorylation. fMLP-induced cellular phospholipase D (PLD) activation 
      was markedly inhibited by DHFC (IC(50) 8.9+/-2.0 microM). In addition, DHFC 
      effectively attenuated the membrane association of protein kinase C (PKC)-alpha, 
      ADP-ribosylation factor (ARF) and Rho A in fMLP-stimulated cells. However, DHFC 
      had no effect on the membrane association of ARF and Rho A caused by guanosine 
      5'-[gamma-thio]triphosphate (GTPgammaS) in cell lysate. fMLP-stimulated protein 
      tyrosine phosphorylation was weakly attenuated by DHFC. DHFC was more efficient 
      in the inhibition of extracellular signal-regulated kinase (ERK) phosphorylation 
      than p38 mitogen-activated protein kinase (MAPK) phosphorylation. Collectively, 
      these results indicate that the suppression of fMLP-induced respiratory burst by 
      DHFC in rat neutrophils is probably mainly attributable to the inhibition of PLD 
      activation, via the blockade of PKC-alpha, ARF and Rho A membrane association.
FAU - Wang, Jih-Pyang
AU  - Wang JP
AD  - Department of Education and Research, Taichung Veterans General Hospital, 407, 
      Taichung, Taiwan, Republic of China. w1994@vghtc.vghtc.gov.tw
FAU - Chang, Ling-Chu
AU  - Chang LC
FAU - Hsu, Mei-Feng
AU  - Hsu MF
FAU - Lin, Chun-Nan
AU  - Lin CN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030820
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (2',5'-dihydroxy-2-furfurylchalcone)
RN  - 0 (Chalcones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Furans)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 5S5A2Q39HX (Chalcone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C beta)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factors)
SB  - IM
MH  - ADP-Ribosylation Factors/metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Chalcone/analogs & derivatives/*pharmacology
MH  - Chalcones
MH  - Cyclic AMP/metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/*pharmacology
MH  - Furans/*pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/*drug effects/enzymology/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phospholipase D/metabolism/*physiology
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Protein Kinase C beta
MH  - Protein Kinase C-alpha
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Respiratory Burst/*drug effects/physiology
MH  - Signal Transduction
MH  - Superoxides/metabolism
EDAT- 2003/08/21 05:00
MHDA- 2004/08/07 05:00
CRDT- 2003/08/21 05:00
PHST- 2003/03/04 00:00 [received]
PHST- 2003/06/27 00:00 [accepted]
PHST- 2003/08/21 05:00 [pubmed]
PHST- 2004/08/07 05:00 [medline]
PHST- 2003/08/21 05:00 [entrez]
AID - 10.1007/s00210-003-0782-8 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):166-74. doi: 
      10.1007/s00210-003-0782-8. Epub 2003 Aug 20.