PMID- 16126002
OWN - NLM
STAT- MEDLINE
DCOM- 20051017
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1736
IP  - 2
DP  - 2005 Sep 15
TI  - Inhibitors of actin polymerisation stimulate arachidonic acid release and 
      5-lipoxygenase activation by upregulation of Ca2+ mobilisation in 
      polymorphonuclear leukocytes involving Src family kinases.
PG  - 109-19
AB  - Here, we show that actin polymerisation inhibitors such as latrunculin B (LB), 
      and to a minor extent also cytochalasin D (Cyt D), enhance the release of 
      arachidonic acid (AA) as well as nuclear translocation of 5-lipoxygenase (5-LO) 
      and 5-LO product synthesis in human polymorphonuclear leukocytes (PMNL), 
      challenged with thapsigargin (TG) or N-formyl-methionyl-leucyl-phenylalanine. The 
      concentration-dependent effects of LB (EC50 approximately 200 nM) declined with 
      prolonged preincubation (>3 min) prior TG and were barely detectable when PMNL 
      were stimulated with Ca2+-ionophores. Investigation of the stimulatory mechanisms 
      revealed that LB (or Cyt D) elicits Ca2+ mobilisation and potentiates 
      stimulus-induced elevation of intracellular Ca2+, regardless of the nature of the 
      stimulus. LB caused rapid but only moderate activation of p38 mitogen-activated 
      protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)2. The 
      selective Src family kinase inhibitors PP2 and SU6656 blocked LB- or Cyt 
      D-mediated Ca2+ mobilisation and suppressed the upregulatory effects on AA 
      release and 5-LO product synthesis, without affecting AA metabolism evoked by 
      ionophore alone. We conclude that in PMNL, inhibitors of actin polymerisation 
      cause enhancement of intracellular Ca2+ levels through Src family kinase 
      signaling, thereby facilitating stimulus-induced release of AA and 5-LO product 
      formation.
FAU - Fischer, Lutz
AU  - Fischer L
AD  - Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie 
      Strasse 9, D-60439 Frankfurt, Germany.
FAU - Poeckel, Daniel
AU  - Poeckel D
FAU - Buerkert, Eva
AU  - Buerkert E
FAU - Steinhilber, Dieter
AU  - Steinhilber D
FAU - Werz, Oliver
AU  - Werz O
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 (Actins)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (Polymers)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidines)
RN  - 22144-77-0 (Cytochalasin D)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - LW7U308U7U (latrunculin B)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Actins/*metabolism
MH  - Adult
MH  - Arachidonate 5-Lipoxygenase/*metabolism
MH  - Arachidonic Acid/*metabolism
MH  - Bridged Bicyclo Compounds, Heterocyclic/metabolism/*pharmacology
MH  - Calcium/*metabolism
MH  - Cytochalasin D/metabolism/*pharmacology
MH  - Enzyme Activation
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Polymers
MH  - Thapsigargin/pharmacology
MH  - Thiazoles/metabolism/*pharmacology
MH  - Thiazolidines
MH  - Up-Regulation
MH  - src-Family Kinases/antagonists & inhibitors/*metabolism
EDAT- 2005/08/30 09:00
MHDA- 2005/10/18 09:00
CRDT- 2005/08/30 09:00
PHST- 2005/04/07 00:00 [received]
PHST- 2005/07/13 00:00 [revised]
PHST- 2005/07/27 00:00 [accepted]
PHST- 2005/08/30 09:00 [pubmed]
PHST- 2005/10/18 09:00 [medline]
PHST- 2005/08/30 09:00 [entrez]
AID - S1388-1981(05)00170-8 [pii]
AID - 10.1016/j.bbalip.2005.07.006 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2005 Sep 15;1736(2):109-19. doi: 
      10.1016/j.bbalip.2005.07.006.