title: Inhibition of c-Src protects paraquat induced microvascular endothelial injury by modulating caveolin-1 phosphorylation and caveolae mediated transcellular permeability.
abstract: The mechanisms underlying paraquat induced acute lung injury (ALI) is still not clear. C-Src plays an important role in the regulation of microvascular endothelial barrier function and the pathogenesis of ALI. In the present study, we found that paraquat induced cell toxicity and an increase of reactive oxygen species (ROS) in endothelium. Paraquat exposure also induced significant increase of caveolin-1 phosphorylation, caveolae trafficking and albumin permeability in endothelial monolayers. C-Src depletion by siRNA significantly attenuate paraquat induced cell toxicity, caveolin-1 phosphorylation, caveolae formation and endothelial hyperpermeability. N-acetylcysteine (NAC) failed to protect endothelial monolayers against paraquat induced toxicity. Thus, our findings suggest that paraquat exposure increases paracellular endothelial permeability by increasing caveolin-1 phosphorylation in a c-Src dependant manner. The depletion of c-Src might protect microvascular endothelial function by regulating caveolin-1 phosphorylation and caveolae trafficking during paraquat exposure, and might have potential therapeutic effects on paraquat induced ALI.
authors.affiliation: Department of Intensive Care Medicine, The Third People's Hospital of Chengdu, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Intensive Care Medicine, The Third People's Hospital of Chengdu, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China; Department of Respiratory Disease, West China Hospital of Sichuan University, Chengdu, China. Electronic address: kk555888@126.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000081247:CSK Tyrosine-Protein Kinase; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D010269:Paraquat / Q000633:toxicity*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D006540:Herbicides; D017382:Reactive Oxygen Species; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D010269:Paraquat; D000111:Acetylcysteine
keywords: Acute lung injury; Caveolin-1; Paraquat; Vascular endothelial barrier; c-Src