PMID- 12237743
OWN - NLM
STAT- MEDLINE
DCOM- 20030421
LR  - 20061115
IS  - 0028-1298 (Print)
IS  - 0028-1298 (Linking)
VI  - 366
IP  - 4
DP  - 2002 Oct
TI  - Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst 
      by cirsimaritin involves inhibition of phospholipase D signaling in rat 
      neutrophils.
PG  - 307-14
AB  - In this study, the cellular localization of the inhibitory effect of a natural 
      flavonoid cirsimaritin against formyl-methionyl-leucyl-phenylalanine 
      (fMLP)-induced respiratory burst in rat neutrophils was investigated. 
      Cirsimaritin concentration-dependently inhibited the superoxide anion 
      (O(*-)(2))generation and O(2) consumption (IC(50) 11.5+/-2.2 micro M and 
      17.0+/-3.9 micro M, respectively) of neutrophils. Cirsimaritin did not reduce, 
      but slightly enhanced the O(*-)(2) generation in phorbol 12-myristate 13-acetate 
      (PMA)-activated or arachidonic acid-stimulated NADPH oxidase preparation as well 
      as during the autoxidation of dihydroxyfumaric acid. Cirsimaritin did not elevate 
      cellular cAMP levels, and only partially inhibited the fMLP-induced [Ca(2+)](i) 
      changes in the presence or absence of extracellular Ca(2+). The phosphorylation 
      of protein tyrosine, extracellular signal-regulated protein kinase and Akt caused 
      by fMLP were attenuated by cirsimaritin in a concentration-dependent manner. In 
      contrast, cirsimaritin had no effect on the phosphorylation of p38 
      mitogen-activated protein kinase. Cirsimaritin produced a concentration-dependent 
      reduction in the formation of phosphatidic acid and phosphatidylethanol, in the 
      presence of ethanol, from fMLP-stimulated neutrophils (IC(50) 15.1+/-6.5 micro M 
      and 15.6+/-3.4 micro M, respectively), but did not affect the phosphatidylethanol 
      formation in response to PMA. Under the similar concentration range, cirsimaritin 
      attenuated the membrane translocation of ARF and Rho A. However, the 
      GTPgammaS-stimulated membrane-associated ARF and Rho in cell lysate were 
      unaffected by cirsimaritin. Collectively, these results indicate that the 
      inhibition of fMLP-induced respiratory burst by cirsimaritin in rat neutrophils 
      is likely mainly through the blockade of phospholipase D signaling pathway.
FAU - Wang, Jih-Pyang
AU  - Wang JP
AD  - Department of Education and Research, Taichung Veterans General Hospital, 
      Taichung 407, Taiwan, Republic of China. w1994@vghtc.vghtc.gov.tw
FAU - Chang, Ling-Chu
AU  - Chang LC
FAU - Hsu, Mei-Feng
AU  - Hsu MF
FAU - Chen, Sheng-Chih
AU  - Chen SC
FAU - Kuo, Sheng-Chu
AU  - Kuo SC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020824
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavones)
RN  - 0 (Flavonoids)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 6601-62-3 (cirsimaritin)
RN  - EC 3.1.4.4 (Phospholipase D)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - *Flavones
MH  - Flavonoids/*pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/*antagonists & inhibitors/pharmacology
MH  - Neutrophils/*drug effects/enzymology
MH  - Phospholipase D/*antagonists & inhibitors/physiology
MH  - Rats
MH  - Respiratory Burst/*drug effects/physiology
MH  - Signal Transduction/drug effects/physiology
EDAT- 2002/09/19 10:00
MHDA- 2003/04/22 05:00
CRDT- 2002/09/19 10:00
PHST- 2002/01/07 00:00 [received]
PHST- 2002/03/28 00:00 [accepted]
PHST- 2002/09/19 10:00 [pubmed]
PHST- 2003/04/22 05:00 [medline]
PHST- 2002/09/19 10:00 [entrez]
AID - 10.1007/s00210-002-0631-1 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2002 Oct;366(4):307-14. doi: 
      10.1007/s00210-002-0631-1. Epub 2002 Aug 24.