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| Status |
Public on Sep 20, 2016 |
| Title |
Expression data from camptothecin-treated rat primary motor neurons |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Topoisomerase 1 (TOP1) poisons like camptothecin (CPT), which are used as chemotherapeutic agents in cancer, elicit DNA damage in quiescient neurons. In this study, we examined the effects of CPT and actinomycin D (ActD) on neuronal cells. Motor (MNs) and cortical (CNs) neurons were more susceptible to the toxic effects of CPT and ActD than fibroblasts. MNs and CNs exhibited a delayed DNA damage response—increase in nuclear γ-H2AX foci—relative to fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts which could explain their enhanced vulnerability to CPT and ActD toxicity. Microarray analysis was performed to identify differentially regulated transcripts in MNs treated with CPT for 2 hours. Many immediate-early genes including Fos and Egr-1 were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cells types treated with CPT; Egr-1 transcript levels, however, were reduced in CPT-treated fibroblasts even though they were elevated in treated MNs and CNs. Pathway and network analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. In conclusion, MNs were more vulnerable than fibroblasts to the damaging effects of TOP1 poisons and they elicit a unique intracellular response to CPT treatment.
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| Overall design |
DIV2 rat primary motor neuron cultures (n=3/treatment) were treated with either 1 microM camptothecin (cpt) or DMSO for 2 hours. Total RNA was isolated from each sample, labeled with biotin and then hybridized on Affymetrix GeneChip Rat Gene 1.0ST arrays.
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| Contributor(s) |
Butchbach ME |
| Citation(s) |
27641670 |
| Submission date |
Mar 22, 2015 |
| Last update date |
Sep 22, 2016 |
| Contact name |
Matthew E R Butchbach |
| E-mail(s) |
Matthew.Butchbach@nemours.org
|
| Organization name |
Nemours Children's Hospital Delaware
|
| Department |
Neurology
|
| Lab |
Motor Neuron Diseases Research Laboratory
|
| Street address |
200 Powder Mill Road, 4462 E400
|
| City |
Wilmington |
| State/province |
DE |
| ZIP/Postal code |
19803 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6247 |
[RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
|
| GSM1640241 |
cpt-treated MNs, biological replicate 1 |
| GSM1640242 |
cpt-treated MNs, biological replicate 2 |
| GSM1640243 |
cpt-treated MNs, biological replicate 3 |
| GSM1640244 |
DMSO-treated MNs, biological replicate 1 |
| GSM1640245 |
DMSO-treated MNs, biological replicate 2 |
| GSM1640246 |
DMSO-treated MNs, biological replicate 3 |
|
| Relations |
| BioProject |
PRJNA279106 |
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