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Cytotoxicity and gene array analysis of alveolar epithelial A549 cells exposed to paraquat.
Chem Biol Interact. 2010 Dec 05; 188(3):427-36.CB

Abstract

Paraquat (PQ), a commonly used herbicide, is highly toxic to humans and animals. The primary injury occurs in the lung, where PQ is actively taken up by alveolar epithelial cells and consequently produces damaging reactive oxygen species (ROS) via redox cycling. ROS have also been shown to induce expression of several early response genes and to activate transcription factors, which may contribute to the inflammatory response associated with PQ injury. In order to further elucidate the mechanism(s) of PQ injury, we investigated its effects on the cellular status and gene expression profile of immortalized human alveolar epithelial A549 cells in vitro. Incubation of cells with PQ resulted in concentration- and time-dependent PQ uptake, which correlated with increases in intracellular ROS levels and decreases in intracellular glutathione content, mitochondrial membrane potential, and cell viability. Gene array analysis showed differential expression in response to PQ exposure over time, particularly increases in: (i) the expression of growth arrest and cell cycle-related genes (e.g. CDKN1A, DDIT3 GADD45A, GDF15, MDM2, EGR1, CASP10, CASP8) and (ii) the expression of pro-inflammatory genes (e.g. IL1A, IL6, IL18, NFKB1, SERPINE1), which correlated with increases in the secretion of pro-inflammatory cytokines (e.g. IL-8, IL-6). These data suggest that uptake of PQ by A549 cells altered the cellular redox status and the expression of several early response genes, including the inflammatory response, all of which might contribute to the overall cytotoxicity of PQ.

Authors+Show Affiliations

Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20883675

Citation

Mitsopoulos, Panagiotis, and Zacharias E. Suntres. "Cytotoxicity and Gene Array Analysis of Alveolar Epithelial A549 Cells Exposed to Paraquat." Chemico-biological Interactions, vol. 188, no. 3, 2010, pp. 427-36.
Mitsopoulos P, Suntres ZE. Cytotoxicity and gene array analysis of alveolar epithelial A549 cells exposed to paraquat. Chem Biol Interact. 2010;188(3):427-36.
Mitsopoulos, P., & Suntres, Z. E. (2010). Cytotoxicity and gene array analysis of alveolar epithelial A549 cells exposed to paraquat. Chemico-biological Interactions, 188(3), 427-36. https://doi.org/10.1016/j.cbi.2010.09.022
Mitsopoulos P, Suntres ZE. Cytotoxicity and Gene Array Analysis of Alveolar Epithelial A549 Cells Exposed to Paraquat. Chem Biol Interact. 2010 Dec 5;188(3):427-36. PubMed PMID: 20883675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytotoxicity and gene array analysis of alveolar epithelial A549 cells exposed to paraquat. AU - Mitsopoulos,Panagiotis, AU - Suntres,Zacharias E, Y1 - 2010/09/29/ PY - 2010/08/23/received PY - 2010/09/16/revised PY - 2010/09/22/accepted PY - 2010/10/2/entrez PY - 2010/10/5/pubmed PY - 2010/12/22/medline SP - 427 EP - 36 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 188 IS - 3 N2 - Paraquat (PQ), a commonly used herbicide, is highly toxic to humans and animals. The primary injury occurs in the lung, where PQ is actively taken up by alveolar epithelial cells and consequently produces damaging reactive oxygen species (ROS) via redox cycling. ROS have also been shown to induce expression of several early response genes and to activate transcription factors, which may contribute to the inflammatory response associated with PQ injury. In order to further elucidate the mechanism(s) of PQ injury, we investigated its effects on the cellular status and gene expression profile of immortalized human alveolar epithelial A549 cells in vitro. Incubation of cells with PQ resulted in concentration- and time-dependent PQ uptake, which correlated with increases in intracellular ROS levels and decreases in intracellular glutathione content, mitochondrial membrane potential, and cell viability. Gene array analysis showed differential expression in response to PQ exposure over time, particularly increases in: (i) the expression of growth arrest and cell cycle-related genes (e.g. CDKN1A, DDIT3 GADD45A, GDF15, MDM2, EGR1, CASP10, CASP8) and (ii) the expression of pro-inflammatory genes (e.g. IL1A, IL6, IL18, NFKB1, SERPINE1), which correlated with increases in the secretion of pro-inflammatory cytokines (e.g. IL-8, IL-6). These data suggest that uptake of PQ by A549 cells altered the cellular redox status and the expression of several early response genes, including the inflammatory response, all of which might contribute to the overall cytotoxicity of PQ. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/20883675/Cytotoxicity_and_gene_array_analysis_of_alveolar_epithelial_A549_cells_exposed_to_paraquat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(10)00568-5 DB - PRIME DP - Unbound Medicine ER -