title: Multiplexed high content screening reveals that cigarette smoke condensate-altered cell signaling pathways are accentuated through FAK inhibition in human bronchial cells.
abstract: The mechanisms by which cigarette smoke condensate (CSC) disrupts F-actin and decreases cell motility in human bronchial (BEAS-2B) cells were assessed. The hypothesis that CSC activated focal adhesion kinase (FAK), mitogen-activated protein kinases (MAPKs), and paxillin in BEAS-2B cells was tested. When BEAS-2B cells were treated with 20 to 100 μg/mL CSC for 1 hour, FAK increased. The CSC caused F-actin disruption, while FAK inhibition alone caused actin aggregates to collapse to the cell periphery, but FAK inhibition combined with CSC caused actin aggregates to distribute throughout the cells. The CSC treatment of BEAS-2B cells showed a dose-dependent increase in the activation of the MAPKs, c-Jun, JNK, ERK, p38, and heat shock protein 27 (Hsp27) and paxillin. Focal adhesion kinase phosphorylation inhibition combined with CSC treatment increased p38 and ERK at 1 hour and 24 hours along with decreased cell number and motility compared with CSC treatment alone. CSC exerts changes in BEAS-2B cells by altering morphology and activating MAPK pathways.
authors.affiliation: Life Sciences, AW Spears Research Center, Greensboro, NC, USA. charleatacarter@yahoo.com
authors.forename: Charleata A
authors.initials: CA
authors.lastname: Carter
mesh_terms: D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018832:Molecular Chaperones; D051419:Paxillin / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D051419:Paxillin; D016755:Proto-Oncogene Proteins c-jun; D014028:Tobacco Smoke Pollution; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020928:Mitogen-Activated Protein Kinases