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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 06, 2008 |
| Title |
Identification of MCIP1 as an ATF6-inducible ER Stress Response Gene in the Heart by Gene Expression Profiling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
We recently found that the endoplasmic reticulum (ER) stress response (ERSR) is activated in surviving cardiac myocytes in a mouse model of in vivo myocardial infarction. ATF6 is an ER stress-activated transcription factor that induces ERSR genes, some of which encode proteins that may protect against ischemic damage. However, few ERSR genes have been identified in the heart, and there have been no gene expression profiling studies of ATF6-inducible genes, in vivo. We previously generated transgenic (TG) mice that express tamoxifen-activated ATF6, ATF6-MER, in the heart; ATF6-MER conferred tamoxifen-dependent ATF6 activation and protection from ischemic damage. To understand of the mechanism of ATF6-mediated cardioprotection, gene expression profiling of ATF6-MER TG mouse hearts was performed. Activated ATF6 changed expression levels of 1,162 genes in the heart; of the 775 ATF6-inducible genes, only 23 are known ERSR genes. One of the genes not expected to be induced by ATF6 is modulatory calcinuerin-interacting protein-1 (MCIP1). MCIP1 is induced in a calcineurin/NFAT-dependent manner during myocardial hypertrophy and it can feedback inhibit cardiomyocyte growth. We found that MCIP1 expression in cultured cardiomyocytes was increased by the prototypical ER stresser, tunicamycin (TM), or by simulated ischemia. Moreover, infecting cardiomyocytes with adenovirus encoding activated ATF6 induced MCIP1 expression and inhibited myocyte growth in response to the alpha 1-adrenergic agonist, phenylephrine. These results suggest that MCIP1 can be induced in the heart by ER stresses, such as ischemia. Moreover, b integrating hypertrophy and ER stress, MCIP-modulated myocyte growth may help rejuvenate nascent ER protein folding, which could contribute to protection from ischemic damage.
Keywords: Gene expression analysis of the effect of activating ATF6 in the hearts of transgenic mice upon treatment with tamoxifen.
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| Overall design |
12 mice were analyzed in this study. Four treatment groups were included in this study: transgenic ATF6-MER mice treated with tamoxifen, transgenic ATF6-MER mice treated with vehicle, nontransgenic littermates treated with tamoxifen, and nontransgenic littermates treated with vehicle. Each treatment group included 3 separate biological replicate samples. Each mouse sampled was male, C57/BL6, ~30 weeks old. Each mouse was treated, then the mouse was sacrificed, the heart was extracted, and left ventricle was isolated. Total RNA was isolated from the left ventricle, and used for hybridization onto an Affymetrix mus 430 2.0 full-genome chip. Each heart was hybridized onto its own chip.
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| Contributor(s) |
Belmont PJ, Tadimalla A, Chen WJ, Martindale JJ, Thuerauf DJ, Gude N, Sussman MA, Glembotski CC |
| Citation(s) |
18319259 |
| Submission date |
Jun 28, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Peter J Belmont |
| Organization name |
Pfizer
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| Street address |
10724 Science Center Drive
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA101307 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8322_RAW.tar |
45.3 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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