Subtoxic and toxic concentrations of benzene and toluene induce Nrf2-mediated antioxidative stress response and affect the central carbon metabolism in lung epithelial cells A549.
Proteomics
; 13(21): 3211-21, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-24108694
ABSTRACT
Since people in industrialized countries spend most of their time indoors, the effects of indoor contaminants such as volatile organic compounds become more and more relevant. Benzene and toluene are among the most abundant compounds in the highly heterogeneous group of indoor volatile organic compounds. 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 Nrf2-mediated and oxidative stress response glycolysis/gluconeogenesis. The occurrence of oxidative stress at nonacute toxic concentrations of benzene and toluene was confirmed by the upregulation of the stress related proteins NQO1 and SOD1. The changes in metabolism were validated by ion chromatography 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 nonacute toxic concentrations on lung epithelial cells. The data provided here will allow for a targeted validation in in vivo models.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toluene
/
Benzene
/
Oxidative Stress
/
Epithelial Cells
/
NF-E2-Related Factor 2
/
Lung
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Proteomics
Journal subject:
BIOQUIMICA
Year:
2013
Type:
Article
Affiliation country:
Germany