p21-activated kinase signaling regulates oxidant-dependent NF-kappa B activation by flow.
Circ Res
; 103(6): 671-9, 2008 Sep 12.
Article
in En
| MEDLINE
| ID: mdl-18669917
ABSTRACT
Disturbed blood flow induces inflammatory gene expression in endothelial cells, which promotes atherosclerosis. Flow stimulates the proinflammatory transcription factor nuclear factor (NF)-kappaB through integrin- and Rac-dependent production of reactive oxygen species (ROS). Previous work demonstrated that NF-kappaB activation by flow is matrix-specific, occurring in cells on fibronectin but not collagen. Activation of p21-activated kinase (PAK) followed the same matrix-dependent pattern. We now show that inhibiting PAK in cells on fibronectin blocked NF-kappaB activation by both laminar and oscillatory flow in vitro and at sites of disturbed flow in vivo. Constitutively active PAK rescued flow-induced NF-kappaB activation in cells on collagen. Surprisingly, PAK was not required for flow-induced ROS production. Instead, PAK modulated the ability of ROS to activate the NF-kappaB pathway. These data demonstrate that PAK controls NF-kappaB activation by modulating the sensitivity of cells to ROS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
NF-kappa B
/
Oxidants
/
P21-Activated Kinases
Limits:
Animals
/
Humans
Language:
En
Journal:
Circ Res
Year:
2008
Document type:
Article
Affiliation country:
United States