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| Status |
Public on Jul 07, 2010 |
| Title |
Differential Regulation of Mitogen-Activated Protein Kinases by Acetaminophen in TAMH cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States. 3’-Hydroxyacetanilide (AMAP), a regioisomer of acetaminophen is useful as a comparative tool for studying APAP-induced toxicity since it is non-toxic relative to APAP. TGF-alpha transgenic mouse hepatocytes were treated with both isomers to investigate mitogen-activated protein kinase cascades in order to differentiate their toxicological outcomes. Mitogen-activated protein kinase (MAPK) cascade expression and activation were measured using microarray and Bioplex technologies, respectively. APAP treatment led to c-Jun N-terminal kinase (JNK) activation, whereas AMAP treatment led to the activation of extracellular-signal-regulated protein kinase (ERK). The microarray data suggested APAP treatment may upregulate gene expression at multiple levels of the JNK cascade including a JNK-related scaffold protein. Expression data was related to phosphoprotein levels using the Bioplex system. APAP treatment led to a significant activation of JNK compared to its regioisomer. In contrast, microarray analysis of AMAP showed a slight upregulation of ERK gene activity. Furthermore, Bioplex data showed AMAP treatment led to significant ERK phosphorylation compared to APAP. Cell viability assays confirmed that APAP-induced activation of JNK was related to higher rates of cell death, whereas activation of ERK by AMAP may be cytoprotective.
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| Overall design |
27 arrays, 9 experimental groups, 2hr AMAP, 2hr APAP, 2hr Control, 6hr AMAP, 6hr APAP, 6hr Control, 24hr AMAP, 24hr APAP, 24hr Control.
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| Contributor(s) |
Beyer RP, Stamper BD, Farin FM, Bammler TK, Nelson SD |
| Citation(s) |
20363829 |
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| Submission date |
Oct 18, 2009 |
| Last update date |
Mar 04, 2019 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
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| Organization name |
University of Washington
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| Department |
Environmental and Occupational Health Sciences
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| Street address |
4225 Roosevelt Way NE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA121443 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE18614_RAW.tar |
119.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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