DIGE-based protein expression analysis of B[a]P-exposed hepatoma cells reveals a complex stress response including alterations in oxidative stress, cell cycle control, and cytoskeleton motility at toxic and subacute concentrations

Franziska Dautel; Stefan Kalkhof; Saskia Trump; Jacob Michaelson; Andreas Beyer; Irina Lehmann; Martin von Bergen

doi:10.1021/pr100723d

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DIGE-based protein expression analysis of B[a]P-exposed hepatoma cells reveals a complex stress response including alterations in oxidative stress, cell cycle control, and cytoskeleton motility at toxic and subacute concentrations

Journal article

Peer reviewed

DIGE-based protein expression analysis of B[a]P-exposed hepatoma cells reveals a complex stress response including alterations in oxidative stress, cell cycle control, and cytoskeleton motility at toxic and subacute concentrations

Franziska Dautel, Stefan Kalkhof, Saskia Trump, Jacob Michaelson, Andreas Beyer, Irina Lehmann and Martin von Bergen

Journal of proteome research, Vol.10(2), pp.379-393

02/04/2011

DOI: 10.1021/pr100723d

PMID: 21171653

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Abstract

Although the effects of high concentrations of the carcinogen benzo[a]pyrene (B[a]P) have been studied extensively, little is known about its effects at subacute toxic concentrations, which are typical for environmental pollutants. We exposed murine Hepa1c1c7 cells to a toxic concentration (5 μM) and a subacute concentration (50 nM) of B[a]P over a period of 2-24 h to differentiate between acute and pseudochronic effects and conducted a time-course analysis of B[a]P-influenced protein expression by DIGE. In total, a set of 120 spots were found to be significantly altered due to B[a]P exposure of which 112 were subsequently identified by mass spectrometry. Clustering and principal component analysis were conducted to identify sets of proteins responding in a concerted manner to the exposure. Our results indicate an immediate response to the contaminant at the protein level and demonstrate that B[a]P exposure alters the cellular response by disturbing proteins involved in oxidative stress, cell cycle regulation, apoptosis, and cytoskeleton organization. Furthermore, network analysis of protein-protein interactions revealed a complex network of interacting, B[a]P-regulated proteins mostly belonging to the cytoskeleton organization and several signal transduction pathways.

Benzo(a)pyrene - toxicity

Apoptosis - drug effects

Humans

Electrophoresis, Gel, Two-Dimensional

Protein Interaction Mapping

Dose-Response Relationship, Drug

Animals

Flow Cytometry

Signal Transduction - drug effects

Databases, Protein

Liver Neoplasms - metabolism

Cell Line, Tumor

Cytoskeleton - metabolism

Mice

Oxidative Stress - drug effects

Cell Cycle - drug effects

Proteome - metabolism

Toxicity Tests

Carcinoma, Hepatocellular - metabolism

Details

Title: Subtitle: DIGE-based protein expression analysis of B[a]P-exposed hepatoma cells reveals a complex stress response including alterations in oxidative stress, cell cycle control, and cytoskeleton motility at toxic and subacute concentrations
Creators: Franziska Dautel - Department of Proteomics, UFZ, Helmholtz-Centre for Environmental Research, Leipzig, Germany
Stefan Kalkhof
Saskia Trump
Jacob Michaelson
Andreas Beyer
Irina Lehmann
Martin von Bergen
Resource Type: Journal article
Publication Details: Journal of proteome research, Vol.10(2), pp.379-393
Publisher: United States
DOI: 10.1021/pr100723d
PMID: 21171653
ISSN: 1535-3893
eISSN: 1535-3907
Language: English
Date published: 02/04/2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984070749702771

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