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Title: Regulation of gene expression during myocardial ischaemia and reperfusion
Author: Hay, Joanna
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2007
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The aim of these studies was to investigate the changes in gene expression that occur in H9c2 myoblast cells subjected to the metabolic stresses associated with myocardial ischaemia/reperfusion. The expression of Vascular Endothelial Growth Factor-A (VEGF-A) and Myocyte Stress 1 protein (ms1) were examined. VEGF-A has a physiological role in stimulating angiogenesis following cardiac ischaemia/reperfusion in vivo, whereas ms1 expression is induced following left ventricular hypertrophy, but has not been examined previously during ischaemia/reperfusion. No increase in VEGF-A, or ms1 mRNA was detected during simulated ischaemia but both were upregulated following reperfusion. The induction in VEGF-A mRNA was caused by an increase in mRNA stability regulated by ERK and JNK pathways. A reporter system was used to demonstrate that simulated ischaemia/reperfusion exerts its effect on both the 5' and 3'UTR of VEGF-A mRNA. The induction in ms1 mRNA was caused by an increase in transcription that was dependent on activation of the JNK pathway. An increase in the amount of ms1 protein expression was also detected during reperfusion. Regulation of translation also influences the expression of proteins during ischaemia/reperfusion. The effect of simulated ischaemia on message translation was investigated using cDNA microarrays. Simulated ischaemia inhibited CAP dependent translation and induced eIF2a phosphorylation. Some messages were more highly represented in the polysome fraction from ischaemic cells, compared to that from resting cells, including FAD oxidoreductase and a sub complex of NADH dehydrogenase, proteins involved in electron transport.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available