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| Status |
Public on Oct 01, 2022 |
| Title |
Integrated stress response couples mitochondria protein translation with oxidative stress control |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Under stress conditions, cells elicit integrated stress response (ISR) to cope with intracellular and extracellular disturbances. However, its role in ischemic heart disease remains to be elucidated. Here, we show that oxygen deprivation in cardiomyocytes triggers significant changes in protein translation. Importantly, ischemia and ischemia/reoxygenation leads to suppression of protein synthesis, which is caused by activation of the PERK/eIF2α axis of ISR. At the functional level, cardiac specific elimination of PERK exacerbates cardiac response to ischemia/reperfusion whereas selective activation of PERK in the heart confers cardioprotection against reperfusion injury. Mechanistically, PERK-mediated improvement in cardiomyocyte survival depends on suppression of protein synthesis and consequently relieves energetic demand on mitochondria. We went further to show that mitochondrial complex components are targeted by protein translation suppression, which significantly diminishes mitochondria-associated production of reactive oxygen species. Indeed, pharmacological activation of ISR protects the heart from ischemia/reperfusion damage, even after the release of occluded coronary artery, highlighting clinical significance for myocardial infarction. Taken together, these findings suggest that ISR improves cell survival through selectively suppressing mitochondrial protein synthesis and reducing oxidative stress in ischemic heart disease.
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| Overall design |
There is 6 sample in this RNA-seq data. The first three sample are replicated sample which belong to control group. Another three sample are also replicated sanples which belong to the PERK overexpression group.All of the samples were treat with stimulated ischemia reperfusion.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/34583519/
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| Contributor(s) |
Zhang G, An YA, Wang ZV, Wang X, Li C, Li Q, Luo X, Deng Y, Gillette TG, Scherer PE |
| Citation(s) |
34583519 |
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| Submission date |
Jun 11, 2021 |
| Last update date |
Jan 09, 2023 |
| Contact name |
GUANGYU ZHANG |
| E-mail(s) |
zgy690511128@gmail.com
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| Phone |
7038142505
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| Organization name |
UTsouthwestern Medical Center
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| Department |
Cardiology
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| Lab |
Zhao Wang Lab
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| Street address |
5323 Harry Hines Blvd
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA736999 |
| SRA |
SRP323779 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE177078_Control_sIR_vs_Perk_sIR.total_genes.xls.gz |
2.0 Mb |
(ftp)(http) |
XLS |
| GSE177078_FPKM.txt.gz |
311.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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