PMID- 11434692
OWN - NLM
STAT- MEDLINE
DCOM- 20020711
LR  - 20220225
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 85
IP  - 6
DP  - 2001 Jun
TI  - Thrombin-induced MCP-1 expression involves activation of the p22phox-containing 
      NADPH oxidase in human vascular smooth muscle cells.
PG  - 1104-10
AB  - Activation of vascular smooth muscle cells (VMSC) by thrombin induces the 
      expression of the chemokine, monocyte chemoattractant protein-1 (MCP-1). We 
      investigated in cultured human and rat VSMC whether reactive oxygen species (ROS) 
      derived from the vascular NADPH oxidase contribute to this effect. Exposure of 
      cultured VSMC to thrombin rapidly increased ROS formation, phosphorylation of p38 
      MAP kinase as well as the expression of MCP-1. Specific inhibition of the p22phox 
      subunit of the vascular NADPH oxidase using either p22phox neutralizing antibody 
      or p22phox antisense oligonucleotides attenuated thrombin-induced ROS generation. 
      Furthermore, thrombin-induced p38 MAP kinase activation as well as MCP-1 
      expression were impaired by antioxidants as well as by p22phox antisense 
      oligonucleotides. Inhibition of p38 MAP kinase diminished the thrombin-induced 
      expression of MCP-1. CONCLUSION: Thrombin, by activating a p22phox-containing 
      NADPH oxidase, elicits ROS generation and activation of p38 MAP kinase in VSMC. 
      The subsequent induction of MCP-1 expression highligts the crucial role of the 
      p22phox-containing NADPH oxidase in thrombin-induced signal transduction in VSMC.
FAU - Brandes, R P
AU  - Brandes RP
AD  - Institut fur Kardiovaskulare Physiologie, Klinikum der JW Goethe-Universitat, 
      Frankfurt/Main, Germany. R.Brandes@em.uni-frankfurt.de
FAU - Viedt, C
AU  - Viedt C
FAU - Nguyen, K
AU  - Nguyen K
FAU - Beer, S
AU  - Beer S
FAU - Kreuzer, J
AU  - Kreuzer J
FAU - Busse, R
AU  - Busse R
FAU - Gorlach, A
AU  - Gorlach A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Chemokine CCL2)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (CYBA protein, human)
RN  - EC 1.6.99.1 (NADPH Dehydrogenase)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - Cell Culture Techniques
MH  - Chemokine CCL2/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Kinetics
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - *Membrane Transport Proteins
MH  - Muscle, Smooth, Vascular/cytology/*drug effects/enzymology/metabolism
MH  - *NADPH Dehydrogenase
MH  - NADPH Oxidases/chemistry/*metabolism/pharmacology
MH  - *Phosphoproteins
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Thrombin/*pharmacology/physiology
EDAT- 2001/07/04 10:00
MHDA- 2002/07/12 10:01
CRDT- 2001/07/04 10:00
PHST- 2001/07/04 10:00 [pubmed]
PHST- 2002/07/12 10:01 [medline]
PHST- 2001/07/04 10:00 [entrez]
AID - 01061104 [pii]
PST - ppublish
SO  - Thromb Haemost. 2001 Jun;85(6):1104-10.