p38 mitogen-activated protein kinase mediates sidestream cigarette smoke-induced endothelial permeability.
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.
Low
Brad
B
Center for Biomedical Research, University of Texas Health Center at Tyler, Tyler, Texas 75708, USA.
Liang
Mei
M
Fu
Jian
J
D015824:Blood-Air Barrier / Q000187:drug effects; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D007093:Imidazoles; D018994:Myosin Light Chains; D011725:Pyridines; D013267:Stilbenes; D014028:Tobacco Smoke Pollution; D048051:p38 Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins; C093642:SB 203580; D000077185:Resveratrol