p38 Mitogen-Activated Protein Kinase Mediates Sidestream Cigarette Smoke-Induced Endothelial Permeability

• Main Authors: Brad Low, Mei Liang, Jian Fu
• Format: Article
• Language: English
• Published: Elsevier 2007-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861319342471

Second-hand smoke is associated with increased risk of cardiovascular diseases. So far, little is known about the signaling mechanisms of second-hand smoke-induced vascular dysfunction. Endothelial junctions are fundamental structures important for maintaining endothelial barrier function. Our study showed that sidestream cigarette smoke (SCS), a major component of second-hand smoke, was able to disrupt endothelial junctions and increase endothelial permeability. Sidestream cigarette smoke stimulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and myosin light chain (MLC). A selective inhibitor of p38 MAPK (SB203580) prevented SCS-induced loss of endothelial barrier integrity as evidenced by transendothelial resistance measurements. Resveratrol, an antioxidant that was able to inhibit SCS-induced p38 MAPK and MLC phosphorylation, also protected endothelial cells from the damage. Thus, p38 MAPK mediates SCS-induced endothelial permeability. Inhibition of p38 MAPK may have therapeutic potential for second-hand smoke-induced vascular injury. Keywords:: myosin light chain (MLC), p38 mitogen-activated protein kinase (MAPK), Rho kinase, endothelial permeability, cigarette smoke