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Gene expression profiling reveals complex changes following MEK-EE expression in cardiac myocytes
Bahareh Badrian1, Marie A Bogoyevitch
1Biochemistry and Molecular Biology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
The International Journal of Biochemistry & Cell Biology
|October 13, 2006
Summary
Prolonged activation of the MEK/ERK pathway in heart cells causes significant gene expression changes, impacting cell structure, metabolism, and apoptosis. This MAPK pathway activation affects diverse cellular functions.
Area of Science:
- Cardiovascular Biology
- Molecular Cell Biology
- Signal Transduction
Background:
- The MEK/ERK pathway promotes proliferative growth in many tissues.
- In cardiac myocytes, ERK pathway activation is associated with hypertrophic growth.
Purpose of the Study:
- To investigate the transcriptional consequences of sustained ERK1/2 activation in cardiac myocytes.
- To analyze gene expression changes induced by MEK-EE overexpression in the heart.
Main Methods:
- Adenoviral overexpression of a constitutively active MEK (MEK-EE) in cardiac myocytes.
- Analysis of gene expression using rat genome microarrays after 24 hours of MEK-EE overexpression.
Main Results:
- Over 2000 gene expression changes were observed, with roughly equal numbers of upregulated and downregulated genes.
- Affected genes were involved in cell structure, metabolism, intracellular signaling, apoptosis, and antioxidant defense.
- Downregulation of antioxidant enzymes including Mn superoxide dismutase, catalase, and thioredoxin 2 was noted.
Conclusions:
- Sustained MEK/ERK pathway activation in cardiac myocytes leads to complex transcriptional reprogramming.
- The mitogen-activated protein kinase (MAPK) pathway significantly impacts diverse cellular functions within the heart.

