PMID- 12383938 OWN - NLM STAT- MEDLINE DCOM- 20021209 LR - 20190610 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1573 IP - 1 DP - 2002 Oct 10 TI - 2-Benzyloxybenzaldehyde inhibits formyl-methionyl-leucyl-phenylalanine stimulation of phospholipase D activation in rat neutrophils. PG - 26-32 AB - 2-Benzyloxybenzaldehyde (CCY1a) inhibited the formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated phospholipase D (PLD)-mediated products, phosphatidic acid (PA) and phosphatidylethanol (PEt) formation in rat neutrophils in a concentration-dependent manner with IC(50) values of 15.8+/-2.5 and 13.9+/-2.0 microM, respectively. The underlying cellular signaling mechanism of CCY1a inhibition was investigated. CCY1a inhibited the plateau phase but not the initial Ca(2+) spike of fMLP-stimulated Ca(2+) signal. CCY1a did not inhibit the [Ca(2+)](i) change in Ca(2+)-free medium in response to fMLP, but inhibited the [Ca(2+)](i) change by the subsequent addition of Ca(2+). In addition, CCY1a treatment attenuated the fMLP-induced protein tyrosine phosphorylation. The membrane translocation of ADP-ribosylation factor (ARF) and Rho A proteins in neutrophils stimulated with fMLP was attenuated by CCY1a in a concentration-dependent manner. In a cell-free system, neither the membrane association of ARF and Rho A caused by GTPgammaS nor the phorbol myristate acetate-stimulated membrane translocation of Rho A was suppressed significantly by CCY1a. These results indicate that the attenuation of protein tyrosine phosphorylation, blockade of Ca(2+) entry, and the suppression of ARF and Rho A membrane translocation are probably obligatory for the CCY1a inhibition of PLD activity in rat neutrophils in response to fMLP. FAU - Wang, Jih-Pyang AU - Wang JP AD - Department of Education and Research, Taichung Veterans General Hospital, 160, Chung Kang Road, Sec. 3, Taiwan, ROC. w1994@vghtc.vghtc.gov.tw FAU - Chang, Ling-Chu AU - Chang LC FAU - Hsu, Mei-Feng AU - Hsu MF 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 - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (2-benzyloxybenzaldehyde) RN - 0 (Benzaldehydes) RN - 0 (Enzyme Inhibitors) RN - 0 (Glycerophospholipids) RN - 0 (Phosphatidic Acids) RN - 0 (phosphatidylethanol) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 3.1.4.4 (Phospholipase D) RN - EC 3.6.5.2 (ADP-Ribosylation Factors) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) RN - SY7Q814VUP (Calcium) SB - IM MH - ADP-Ribosylation Factors/metabolism MH - Animals MH - Benzaldehydes/*pharmacology MH - Calcium/metabolism MH - Cell Membrane/drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Glycerophospholipids/metabolism MH - N-Formylmethionine Leucyl-Phenylalanine/antagonists & inhibitors/*pharmacology MH - Neutrophils/*drug effects/metabolism MH - Phosphatidic Acids/metabolism MH - Phospholipase D/antagonists & inhibitors/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - rhoA GTP-Binding Protein/metabolism EDAT- 2002/10/18 04:00 MHDA- 2002/12/10 04:00 CRDT- 2002/10/18 04:00 PHST- 2002/10/18 04:00 [pubmed] PHST- 2002/12/10 04:00 [medline] PHST- 2002/10/18 04:00 [entrez] AID - S030441650200329X [pii] AID - 10.1016/s0304-4165(02)00329-x [doi] PST - ppublish SO - Biochim Biophys Acta. 2002 Oct 10;1573(1):26-32. doi: 10.1016/s0304-4165(02)00329-x.