PMID- 12663040
OWN - NLM
STAT- MEDLINE
DCOM- 20030501
LR  - 20211203
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 65
IP  - 7
DP  - 2003 Apr 1
TI  - Investigation of the cellular mechanism of inhibition of 
      formyl-methionyl-leucyl-phenylalanine-induced superoxide anion generation in rat 
      neutrophils by 2-benzyloxybenzaldehyde.
PG  - 1043-51
AB  - The inhibition of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide 
      anion (O2(.-)) generation by 2-benzyloxybenzaldehyde (CCY1a) was investigated in 
      rat neutrophils, and the underlying mechanism of this inhibition was assessed. 
      CCY1a concentration-dependently inhibited O2(.-) generation (IC(50)=18.5+/-4.3 
      microM). In cell-free systems, CCY1a failed to alter O2(.-) generation during 
      dihydroxyfumaric acid autoxidation, in phorbol 12-myristate 13-acetate 
      (PMA)-activated neutrophil particulate NADPH oxidase preparations, or during 
      arachidonic acid-induced NADPH oxidase activation. CCY1a increased cellular 
      cyclic AMP (cAMP) levels in a time- and concentration-dependent manner, and this 
      cAMP-elevating effect was inhibited by the adenylyl cyclase inhibitor 
      9-(tetrahydro-2'-furyl)adenine (SQ22536), adenosine deaminase (ADA), and the 
      adenosine receptor antagonist 8-(p-sulfophenyl)theophylline. In neutrophils, 
      inhibition of O2(.-) generation by CCY1a was partially reversed by the protein 
      kinase A inhibitor 
      (9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-l][1,6]benzodiazocine-10-carboxylic 
      acid, hexyl ester (KT5720). CCY1a did not affect fMLP-induced p38 
      mitogen-activated protein kinase phosphorylation, but concentration-dependently 
      attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) and 
      Akt (IC(50) about 31.3 and 19.4 microM, respectively). The plateau phase, but not 
      the initial spike, of fMLP-induced [Ca2+](i) changes was inhibited by CCY1a in a 
      concentration-dependent manner. CCY1a inhibition of Ca2+ entry, ERK, and Akt 
      phosphorylation was not prevented by SQ22536 or ADA. fMLP-induced phospholipase D 
      (PLD) activation was inhibited by CCY1a (IC(50)=13.9+/-2.0 microM). ADA and 
      KT5720 did not prevent the inhibition of PLD activation by CCY1a. Collectively, 
      these results indicate that the inhibition by CCY1a of fMLP-induced O2(.-) 
      generation in rat neutrophils can probably be attributed to the increase in cAMP 
      levels, and to the blockade of Ca2+ entry, suppression of Akt, and PLD activation 
      via cAMP-independent mechanisms.
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 - Lin, Yi-Lee
AU  - Lin YL
FAU - Hsu, Mei-Feng
AU  - Hsu MF
FAU - Chang, Chiung-Yun
AU  - Chang CY
FAU - Huang, Li-Jiau
AU  - Huang LJ
FAU - Kuo, Sheng-Chu
AU  - Kuo SC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (2-benzyloxybenzaldehyde)
RN  - 0 (Benzaldehydes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 65929-03-5 (formylmethionyl-leucyl-phenylalanine methyl ester)
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 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Benzaldehydes/*pharmacology
MH  - Calcium/metabolism
MH  - Cyclic AMP/*metabolism
MH  - Drug Interactions
MH  - Enzyme Activation
MH  - In Vitro Techniques
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/*analogs & derivatives/*pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Phospholipase D/metabolism
MH  - Phosphorylation/drug effects
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Superoxides/*metabolism
EDAT- 2003/03/29 05:00
MHDA- 2003/05/02 05:00
CRDT- 2003/03/29 05:00
PHST- 2003/03/29 05:00 [pubmed]
PHST- 2003/05/02 05:00 [medline]
PHST- 2003/03/29 05:00 [entrez]
AID - S0006295203000066 [pii]
AID - 10.1016/s0006-2952(03)00006-6 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2003 Apr 1;65(7):1043-51. doi: 10.1016/s0006-2952(03)00006-6.