PMID- 19697962
OWN - NLM
STAT- MEDLINE
DCOM- 20100201
LR  - 20151119
IS  - 1535-3907 (Electronic)
IS  - 1535-3893 (Linking)
VI  - 8
IP  - 10
DP  - 2009 Oct
TI  - Toponomics analysis of drug-induced changes in arachidonic acid-dependent 
      signaling pathways during spinal nociceptive processing.
PG  - 4851-9
LID - 10.1021/pr900106v [doi]
AB  - Multi-Epitope-Ligand-Carthography (MELC) allows consecutive immunohistochemical 
      visualization of up to 100 proteins on the same tissue sample. Subsequent 
      biomathematical analysis of these images allows a quantitative description of 
      changes in protein networks. We used the MELC technology to study the effect of 
      the nonopioid analgesic drug dipyrone on protein network profiles associated with 
      arachidonic acid-dependent signaling pathways. MELC analysis with 31 different 
      fluorescence-labeled tags was used to compare the effect of dipyrone on protein 
      networks in spinal cords of mice with zymosan-induced hyperalgesia, a common 
      model for inflammatory pain. We found that the number of motifs which describe 
      the colocalization of 5-lipoxygenase (5-LO) or 12-LO with other proteins 
      increased disproportionally after dipyrone treatment. Activation of 5-LO and 
      12-LO induces their translocation to membrane compartments which was also 
      reflected by MELC results. Although no changes in 5-LO or 12-LO expression were 
      seen by Western blot analysis or by immunohistochemistry in spinal cords of 
      dipyrone-treated mice, the activation of both enzymes was verified by determining 
      LO-products. Spinal amounts of 5(S)-hydroxyeicosatetraenoic acid (HETE) and 
      12(S)-HETE, which are generated by 5-LO and 12-LO, respectively, were 
      significantly increased in spinal cords of dipyrone-treated animals. In primary 
      spinal cord neurons, dipyrone selectively and dose-dependently increased 
      5(S)-(HETE) and 12(S)-HETE synthesis. Thus, we show for the first time that 
      monitoring protein network profiles by topological proteomic analysis is a useful 
      tool to identify mechanisms of drug actions.
FAU - Linke, Bona
AU  - Linke B
AD  - Pharmazentrum Frankfurt, ZAFES, Institute of Clinical Pharmacology, Klinikum der 
      Goethe-Universitat Frankfurt, Germany.
FAU - Pierre, Sandra
AU  - Pierre S
FAU - Coste, Ovidiu
AU  - Coste O
FAU - Angioni, Carlo
AU  - Angioni C
FAU - Becker, Wiebke
AU  - Becker W
FAU - Maier, Thorsten Jurgen
AU  - Maier TJ
FAU - Steinhilber, Dieter
AU  - Steinhilber D
FAU - Wittpoth, Claus
AU  - Wittpoth C
FAU - Geisslinger, Gerd
AU  - Geisslinger G
FAU - Scholich, Klaus
AU  - Scholich K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Proteome Res
JT  - Journal of proteome research
JID - 101128775
RN  - 0 (Proteome)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 6429L0L52Y (Dipyrone)
RN  - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
SB  - IM
MH  - Animals
MH  - Arachidonate 12-Lipoxygenase/metabolism
MH  - Arachidonate 5-Lipoxygenase/metabolism
MH  - Arachidonic Acid/*metabolism
MH  - Dipyrone/*pharmacology
MH  - Immunohistochemistry/methods
MH  - Mice
MH  - Nociceptors/*metabolism
MH  - Prostaglandin-Endoperoxide Synthases/metabolism
MH  - Proteome/drug effects
MH  - Proteomics/*methods
MH  - Signal Transduction/*drug effects
MH  - Spinal Cord/cytology/ultrastructure
MH  - Statistics, Nonparametric
EDAT- 2009/08/25 09:00
MHDA- 2010/02/02 06:00
CRDT- 2009/08/25 09:00
PHST- 2009/08/25 09:00 [entrez]
PHST- 2009/08/25 09:00 [pubmed]
PHST- 2010/02/02 06:00 [medline]
AID - 10.1021/pr900106v [doi]
PST - ppublish
SO  - J Proteome Res. 2009 Oct;8(10):4851-9. doi: 10.1021/pr900106v.