PMID- 21487675
OWN - NLM
STAT- MEDLINE
DCOM- 20120315
LR  - 20211020
IS  - 1432-1440 (Electronic)
IS  - 0946-2716 (Linking)
VI  - 89
IP  - 8
DP  - 2011 Aug
TI  - The endothelium-derived contracting factor uridine adenosine tetraphosphate 
      induces P2Y(2)-mediated pro-inflammatory signaling by monocyte chemoattractant 
      protein-1 formation.
PG  - 799-810
LID - 10.1007/s00109-011-0750-6 [doi]
AB  - It is very well established that purinergic signaling plays a relevant role in 
      vascular physiology and pathophysiology. Recently, a new purinoceptor agonist 
      uridine adenosine tetraphosphate (Up(4)A) has been identified as a highly potent 
      endothelial-derived contracting factor (EDCF). The purpose of the study was to 
      investigate Up(4)A's influence on pro-inflammatory mechanisms. An early component 
      of the inflammatory response in atherogenesis is the oxidative stress-induced 
      formation of monocyte chemoattractant protein-1 (MCP-1). Here, we investigated 
      the influence of Up(4)A on MCP-1 formation and characterized the underlying 
      signaling transduction mechanisms in rat vascular smooth muscle cells (VSMCs). 
      Up(4)A induced MCP-1 expression and secretion in VSMCs via the activation of 
      P2Y(2) in a concentration-dependent manner. MCP-1 formation depends on generation 
      of reactive oxygen species (ROS). To determine whether the predominant source of 
      ROS in the vasculature, the NAD(P)H oxidase (Nox), is involved, we used different 
      approaches. The ROS scavenger, tiron, the Nox inhibitor, apocynin and 
      diphenyl-iodonium, as well as Nox1 knockdown, diminished the Up(4)A-induced MCP-1 
      formation. Rac1 activation and p47(phox) translocation from cytosol to the plasma 
      membrane-both required for assembling and activation of Nox, were stimulated by 
      Up(4)A. ERK1/2 and p38 activation is essential for the intracellular signal 
      transduction. In summary, Up(4)A induced Nox1-dependent ROS generation, which 
      further stimulated MCP-1 formation via MAPK phosphorylation in VSMCs. This 
      process requires the activation of the G-protein coupled receptor P2Y(2). 
      Therefore, Up(4)A is not only a potent EDCF but also a potent inductor of 
      pro-inflammatory response in the vascular wall.
FAU - Schuchardt, Mirjam
AU  - Schuchardt M
AD  - Charite-Universitatsmedizin Berlin; Med. Klinik mit SP Nephrologie, Campus 
      Benjamin Franklin, Berlin, Germany.
FAU - Prufer, Jasmin
AU  - Prufer J
FAU - Prufer, Nicole
AU  - Prufer N
FAU - Wiedon, Annette
AU  - Wiedon A
FAU - Huang, Tao
AU  - Huang T
FAU - Chebli, Miriam
AU  - Chebli M
FAU - Jankowski, Vera
AU  - Jankowski V
FAU - Jankowski, Joachim
AU  - Jankowski J
FAU - Schafer-Korting, Monika
AU  - Schafer-Korting M
FAU - Zidek, Walter
AU  - Zidek W
FAU - van der Giet, Markus
AU  - van der Giet M
FAU - Tolle, Markus
AU  - Tolle M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110413
PL  - Germany
TA  - J Mol Med (Berl)
JT  - Journal of molecular medicine (Berlin, Germany)
JID - 9504370
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dinucleoside Phosphates)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 0 (uridine adenosine tetraphosphate)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 1.6.3.- (NADPH Oxidase 1)
RN  - EC 1.6.3.- (NOX1 protein, rat)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Chemokine CCL2/*metabolism
MH  - Dinucleoside Phosphates/*pharmacology
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Inflammation Mediators/*metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Monocytes/drug effects/metabolism
MH  - Myocytes, Smooth Muscle/cytology/drug effects/enzymology
MH  - NADH, NADPH Oxidoreductases/metabolism
MH  - NADPH Oxidase 1
MH  - Nitrates/metabolism
MH  - Nitrites/metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Purinergic P2Y2/*metabolism
MH  - Signal Transduction/*drug effects
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
MH  - rac1 GTP-Binding Protein/metabolism
EDAT- 2011/04/14 06:00
MHDA- 2012/03/16 06:00
CRDT- 2011/04/14 06:00
PHST- 2010/10/07 00:00 [received]
PHST- 2011/03/04 00:00 [accepted]
PHST- 2011/03/02 00:00 [revised]
PHST- 2011/04/14 06:00 [entrez]
PHST- 2011/04/14 06:00 [pubmed]
PHST- 2012/03/16 06:00 [medline]
AID - 10.1007/s00109-011-0750-6 [doi]
PST - ppublish
SO  - J Mol Med (Berl). 2011 Aug;89(8):799-810. doi: 10.1007/s00109-011-0750-6. Epub 
      2011 Apr 13.