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Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells.
Toxicology. 2009 Jul 10; 261(3):89-102.T

Abstract

Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-kappaB (NF-kappaB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-alpha and NF-kappaB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30mug/ml CSC significantly activated PKC-alpha, while CSC doses above 20mug/ml CSC significantly activated NF-kappaB. As NF-kappaB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30mug/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30mug/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-alpha, NF-kappaB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases.

Authors+Show Affiliations

A.W. Spears Research Center, 420 N. English Street, Lorillard Tobacco Company, Greensboro, NC 27405, USA. charleatacarter@lortobco.comNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19394402

Citation

Carter, Charleata A., and Jonathan T. Hamm. "Multiplexed Quantitative High Content Screening Reveals That Cigarette Smoke Condensate Induces Changes in Cell Structure and Function Through Alterations in Cell Signaling Pathways in Human Bronchial Cells." Toxicology, vol. 261, no. 3, 2009, pp. 89-102.
Carter CA, Hamm JT. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells. Toxicology. 2009;261(3):89-102.
Carter, C. A., & Hamm, J. T. (2009). Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells. Toxicology, 261(3), 89-102. https://doi.org/10.1016/j.tox.2009.04.039
Carter CA, Hamm JT. Multiplexed Quantitative High Content Screening Reveals That Cigarette Smoke Condensate Induces Changes in Cell Structure and Function Through Alterations in Cell Signaling Pathways in Human Bronchial Cells. Toxicology. 2009 Jul 10;261(3):89-102. PubMed PMID: 19394402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells. AU - Carter,Charleata A, AU - Hamm,Jonathan T, Y1 - 2009/04/24/ PY - 2009/02/11/received PY - 2009/04/06/revised PY - 2009/04/15/accepted PY - 2009/4/28/entrez PY - 2009/4/28/pubmed PY - 2009/7/10/medline SP - 89 EP - 102 JF - Toxicology JO - Toxicology VL - 261 IS - 3 N2 - Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-kappaB (NF-kappaB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-alpha and NF-kappaB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30mug/ml CSC significantly activated PKC-alpha, while CSC doses above 20mug/ml CSC significantly activated NF-kappaB. As NF-kappaB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30mug/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30mug/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-alpha, NF-kappaB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/19394402/Multiplexed_quantitative_high_content_screening_reveals_that_cigarette_smoke_condensate_induces_changes_in_cell_structure_and_function_through_alterations_in_cell_signaling_pathways_in_human_bronchial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(09)00215-7 DB - PRIME DP - Unbound Medicine ER -