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Cardiac myocyte gene expression profiling during H₂O₂-induced apoptosis

National Heart and Lung Institute Division, Faculty of Medicine, Imperial College London, London, United Kingdom

High levels of oxidative stress promote cardiac myocyte death, though lower levels are potentially cytoprotective/anabolic. We examined the changes in gene expression in rat neonatal cardiac myocytes exposed to apoptotic (0.2 mM) or nontoxic (0.04 mM) concentrations of H₂O₂ (2, 4, or 24 h) using Affymetrix microarrays. Using U34B arrays, we identified a ubiquitously expressed, novel H₂O₂-responsive gene [putative peroxide-inducible transcript 1 (Perit1)], which generates two alternatively spliced transcripts. Using 230 2.0 arrays, H₂O₂ (0.04 mM) promoted significant changes in expression of only 32 genes, all of which were seen with 0.2 mM H₂O₂. We failed to detect any increase in the rate of protein synthesis in cardiac myocytes exposed to <0.1 mM H₂O₂, further suggesting that global, low concentrations of H₂O₂ are not anabolic in this system. H₂O₂ (0.2 mM) promoted significant (P < 0.05, >1.75-fold) changes in expression of 649 mRNAs and 187 RNAs corresponding to no established gene. Of the mRNAs, 114 encoded transcriptional regulators including Krüppel-like factors (Klfs). Quantitative PCR independently verified the changes in Klf expression. Thus, H₂O₂-induced cardiac myocyte apoptosis is associated with dynamic changes in gene expression. The expression of these genes and their protein products potentially influences the progression of the apoptotic response.

microarrays; Krüppel-like factors; Perit1; oxidative stress

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