Key result
UV radiation induces the most gene expression changes in neonatal rat cardiac cells among tested stressors.
Why the study?
The stress response of cardiac cells to mechanical stress compared to genotoxic stresses induced by DNA damaging agents was not well characterized.
Gene expression responses to mechanical stress, ionizing radiation, and UV radiation in cardiac cells exhibit high stressor and cell-type specificity.
Stressor- and cell-specific gene responses in neonatal rat cardiac cells; hypothesis-generating for human cardiac stress biology and leaves open clinical translation.
BACKGROUND: During excessive pressure or volume overload, cardiac cells are subjected to increased mechanical stress (MS). We set out to investigate how the stress response of cardiac cells to MS can be compared to genotoxic stresses induced by DNA damaging agents. We chose for this purpose to use ionising radiation (IR), which during mediastinal radiotherapy can result in cardiac tissue remodelling and diminished heart function, and ultraviolet radiation (UV) that in contrast to IR induces high concentrations of DNA replication- and transcription-blocking lesions. RESULTS: Cultures enriched for neonatal rat cardiac myocytes (CM) or fibroblasts were subjected to any one of the three stressors. Affymetrix microarrays, analysed with Linear Modelling on Probe Level, were used to determine gene expression patterns at 24 hours after (the start of) treatment. The numbers of differentially expressed genes after UV were considerably higher than after IR or MS. Remarkably, after all three stressors the predominant gene expression response in CM-enriched fractions was up-regulation, while in fibroblasts genes were more frequently down-regulated. To investigate the activation or repression of specific cellular pathways, genes present on the array were assigned to 25 groups, based on their biological function. As an example, in the group of cholesterol biosynthesis a significant proportion of genes was up-regulated in CM-enriched fractions after MS, but down-regulated after IR or UV. CONCLUSION: Gene expression responses after the types of cellular stress investigated (MS, IR or UV) have a high stressor and cell type specificity.
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Boerma et al. (2005) studied Cellular stress response in cardiac cells. Mechanical stress, ionising radiation, or ultraviolet radiation vs. Untreated controls was evaluated on Differentially expressed genes (up-regulated or down-regulated). Gene expression responses in neonatal rat cardiac myocytes and fibroblasts after mechanical stress, ionising radiation, or ultraviolet radiation showed high stressor and cell-type specificity, with UV inducing the highest number of differentially expressed genes.
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