Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1021/pr500957t |
| Title (Primary) | Pathway and time-resolved benzo[a]pyrene toxicity on Hepa1c1c7 cells at toxic and subtoxic exposure |
| Author | Kalkhof, S.; Dautel, F.; Loguercio, S.; Baumann, S.; Trump, S.; Jungnickel, H.; Otto, W.; Rudzok, S.; Potratz, S.; Luch, A.; Lehmann, I.; Beyer, A.; von Bergen, M. |
| Source Titel | Journal of Proteome Research |
| Year | 2015 |
| Department | IMMU; METABOX; PROTEOM |
| Volume | 14 |
| Issue | 1 |
| Page From | 164 |
| Page To | 182 |
| Language | englisch |
| Keywords | Benzo[a]pyrene (B[a]P); aryl hydrocarbon receptor (Ahr); oxidative stress; protein expression analysis; SILAC; proteomics; metabolomics; Hepa1c1c7 cells; B[a]P metabolites |
| UFZ wide themes | RU3; |
| Abstract | Benzo[a]pyrene (B[a]P) is an environmental contaminant mainly studied for its toxic/carcinogenic effects. For a comprehensive and pathway orientated mechanistic understanding of the effects directly triggered by a toxic (5 μM) or a subtoxic (50 nM) concentration of B[a]P or indirectly by its metabolites, we conducted time series experiments for up to 24 h to study the effects in murine hepatocytes. These cells rapidly take up and actively metabolize B[a]P, which was followed by quantitative analysis of the concentration of intracellular B[a]P and seven representative degradation products. Exposure with 5 μM B[a]P led to a maximal intracellular concentration of 1604 pmol/5 × 104 cells, leveling at 55 pmol/5 × 104 cells by the end of the time course. Changes in the global proteome (>1000 protein profiles) and metabolome (163 metabolites) were assessed in combination with B[a]P degradation. Abundance profiles of 236 (both concentrations), 190 (only 5 μM), and 150 (only 50 nM) proteins were found to be regulated in response to B[a]P in a time-dependent manner. At the endogenous metabolite level amino acids, acylcarnitines and glycerophospholipids were particularly affected by B[a]P. The comprehensive chemical, proteome and metabolomic data enabled the identification of effects on the pathway level in a time-resolved manner. So in addition to known alterations, also protein synthesis, lipid metabolism, and membrane dysfunction were identified as B[a]P specific effects. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=15476 |
| Kalkhof, S., Dautel, F., Loguercio, S., Baumann, S., Trump, S., Jungnickel, H., Otto, W., Rudzok, S., Potratz, S., Luch, A., Lehmann, I., Beyer, A., von Bergen, M. (2015): Pathway and time-resolved benzo[a]pyrene toxicity on Hepa1c1c7 cells at toxic and subtoxic exposure J. Proteome Res. 14 (1), 164 - 182 10.1021/pr500957t |
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