Pathway and Time-Resolved Benzo[a]pyrene Toxicity on Hepa1c1c7 Cells at Toxic and Subtoxic Exposure
详细信息 查看全文
- 作者：Stefan Kalkhof ; Franziska Dautel ; Salvatore Loguercio ; Sven Baumann ; Saskia Trump ; Harald Jungnickel ; Wolfgang Otto ; Susanne Rudzok ; Sarah Potratz ; Andreas Luch ; Irina Lehmann ; Andreas Beyer ; Martin von Bergen
- 刊名：Journal of Proteome Research
- 出版年：2015
- 出版时间：January 2, 2015
- 年：2015
- 卷：14
- 期：1
- 页码：164-182
- 全文大小：630K
- ISSN：1535-3907
文摘
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 渭M) 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 渭M B[a]P led to a maximal intracellular concentration of 1604 pmol/5 脳 104 cells, leveling at 55 pmol/5 脳 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 渭M), 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.