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Titel (primär) Subtoxic and toxic concentrations of benzene and toluene induce Nrf-2 mediated anti-oxidative stress response and affect the central carbon metabolism in lung epithelial cells A549
Autor Murugesan, K.; Baumann, S.; Wissenbach, D.K.; Kliemt, S.; Kalkhof, S.; Otto, W.; Mögel, I.; Kohajda, T.; von Bergen, M.; Tomm, J.M.;
Journal / Serie Proteomics
Erscheinungsjahr 2013
Department IMMU; METABOX; PROTEOM;
Band/Volume 13
Heft 21
Sprache englisch;
POF III (gesamt) F11;
UFZ Querschnittsthemen ru3
Abstract Since people in industrialized countries spend most of their time indoors the effects of indoor contaminants like volatile organic compounds (VOCs) become more and more relevant. Benzene and toluene are among the most abundant compounds in the highly heterogeneous group of indoor VOCs. In order to understand their effects on lung epithelial cells (A549) representing lung's first line of defense, we chose a global proteome and a targeted metabolome approach in order to detect adverse outcome pathways caused by exposure to benzene and toluene. Using a DIGE approach, 93 of 469 detected protein spots were found to be differentially expressed after exposure to benzene, and 79 of these spots were identified by MS. Pathway analysis revealed an enrichment of proteins involved in Nrf-2 mediated and oxidative stress response glycolysis/gluconeogenesis. The occurrence of oxidative stress at non-acute toxic concentrations of benzene and toluene was confirmed by the up regulation of the stress related proteins NQO1 and SOD1. The changes in metabolism were validated by IC-MS/MS analysis revealing significant changes of glucose-6-phosphate, fructose-6-phosphate, 3-phosphoglycerate and NADPH. The molecular alterations identified as a result of benzene and toluene exposure demonstrate the detrimental effect of non-acute toxic concentrations on lung epithelial cells. The data provided here will allow for a targeted validation in in vivo models.
ID 14108
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=14108
Murugesan, K., Baumann, S., Wissenbach, D.K., Kliemt, S., Kalkhof, S., Otto, W., Mögel, I., Kohajda, T., von Bergen, M., Tomm, J.M. (2013):
Subtoxic and toxic concentrations of benzene and toluene induce Nrf-2 mediated anti-oxidative stress response and affect the central carbon metabolism in lung epithelial cells A549
Proteomics 13 (21), 3211 - 3221