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Sphingosine 1-phosphate antagonizes human neutrophil apoptosis via p38 mitogen-activated protein kinase.

Chihab, Rifki LU ; Ares, Isabella LU ; Alvarado-Kristensson, Maria LU and Andersson, Tommy LU (2003) In Cellular and Molecular Life Sciences1997-01-01+01:00 60(4). p.776-785
Abstract
Sphingosine 1-phosphate (SPP) is associated with the regulation of apoptosis, although its role in neutrophil apoptosis remains poorly investigated. Here, we show that exogenous SPP antagonizes spontaneous and anti-Fas-induced apoptosis in neutrophils. Pre-treatment with pertussis toxin clearly reduced the apoptosis-inhibiting capacity of SPP. Consequently, we investigated the involvement of potential modulators of apoptosis that are activated downstream of Gi/G0-coupled receptors. Neither Akt activity nor change in basal activity of c-Jun N-terminal kinases was detected during apoptosis or after adding SPP. In contrast, there was a transient decrease in phosphorylation of both extracellular-regulated kinase (ERK) and p38mitogen-activated... (More)
Sphingosine 1-phosphate (SPP) is associated with the regulation of apoptosis, although its role in neutrophil apoptosis remains poorly investigated. Here, we show that exogenous SPP antagonizes spontaneous and anti-Fas-induced apoptosis in neutrophils. Pre-treatment with pertussis toxin clearly reduced the apoptosis-inhibiting capacity of SPP. Consequently, we investigated the involvement of potential modulators of apoptosis that are activated downstream of Gi/G0-coupled receptors. Neither Akt activity nor change in basal activity of c-Jun N-terminal kinases was detected during apoptosis or after adding SPP. In contrast, there was a transient decrease in phosphorylation of both extracellular-regulated kinase (ERK) and p38mitogen-activated protein kinase (MAPK) during both spontaneous and anti-Fas-induced apoptosis. Although exogenous SPP reversed these reductions in kinase activity, experiments with inhibitors of ERK (PD98059) and p38 MAPK (SB203580) revealed that only SB203580 counteracted the effect of SPP. Thus, SPP counteracts neutrophil apoptosis via a Gi/G0protein survival-signalling pathway that includes modulation of p38 MAPK activity. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
Neutrophils: physiology, Apoptosis: drug effects, Apoptosis: physiology, Enzyme Inhibitors: pharmacology, Flavones: pharmacology, Human, Imidazoles: pharmacology, Mitogen-Activated Protein Kinases: antagonists & inhibitors, Mitogen-Activated Protein Kinases: metabolism, Phosphorylation, Pyridines: pharmacology, Signal Transduction: physiology, Sphingosine: analogs & derivatives, Sphingosine: metabolism, Support, Non-U.S. Gov't
in
Cellular and Molecular Life Sciences1997-01-01+01:00
volume
60
issue
4
pages
776 - 785
publisher
Birkhaüser
external identifiers
  • pmid:12785724
  • wos:000183175900012
  • scopus:0038702407
ISSN
1420-9071
DOI
10.1007/s00018-003-2357-8
language
English
LU publication?
yes
id
a4c15695-f343-4fcc-a85c-f554b132a5e8 (old id 116176)
date added to LUP
2007-07-24 13:14:18
date last changed
2018-05-29 11:30:28
@article{a4c15695-f343-4fcc-a85c-f554b132a5e8,
  abstract     = {Sphingosine 1-phosphate (SPP) is associated with the regulation of apoptosis, although its role in neutrophil apoptosis remains poorly investigated. Here, we show that exogenous SPP antagonizes spontaneous and anti-Fas-induced apoptosis in neutrophils. Pre-treatment with pertussis toxin clearly reduced the apoptosis-inhibiting capacity of SPP. Consequently, we investigated the involvement of potential modulators of apoptosis that are activated downstream of Gi/G0-coupled receptors. Neither Akt activity nor change in basal activity of c-Jun N-terminal kinases was detected during apoptosis or after adding SPP. In contrast, there was a transient decrease in phosphorylation of both extracellular-regulated kinase (ERK) and p38mitogen-activated protein kinase (MAPK) during both spontaneous and anti-Fas-induced apoptosis. Although exogenous SPP reversed these reductions in kinase activity, experiments with inhibitors of ERK (PD98059) and p38 MAPK (SB203580) revealed that only SB203580 counteracted the effect of SPP. Thus, SPP counteracts neutrophil apoptosis via a Gi/G0protein survival-signalling pathway that includes modulation of p38 MAPK activity.},
  author       = {Chihab, Rifki and Ares, Isabella and Alvarado-Kristensson, Maria and Andersson, Tommy},
  issn         = {1420-9071},
  keyword      = {Neutrophils: physiology,Apoptosis: drug effects,Apoptosis: physiology,Enzyme Inhibitors: pharmacology,Flavones: pharmacology,Human,Imidazoles: pharmacology,Mitogen-Activated Protein Kinases: antagonists & inhibitors,Mitogen-Activated Protein Kinases: metabolism,Phosphorylation,Pyridines: pharmacology,Signal Transduction: physiology,Sphingosine: analogs & derivatives,Sphingosine: metabolism,Support,Non-U.S. Gov't},
  language     = {eng},
  number       = {4},
  pages        = {776--785},
  publisher    = {Birkhaüser},
  series       = {Cellular and Molecular Life Sciences1997-01-01+01:00},
  title        = {Sphingosine 1-phosphate antagonizes human neutrophil apoptosis via p38 mitogen-activated protein kinase.},
  url          = {http://dx.doi.org/10.1007/s00018-003-2357-8},
  volume       = {60},
  year         = {2003},
}