Regulatory mechanism of cellular iron metabolism on aspirin resistance to oxidative damage / 中国病理生理杂志

ABSTRACT

AIM: To explore the regulatory effects of ferritin expression and intracellular iron change on aspirin resistance to oxidative damage in endothelial cells. METHODS: Using ELISA to measure the levels of ferritin expression under different aspirin concentrations, in the presence of iron cheltor desferioxamine and add to FeCl 3. Then using RNA-protein bandshift assay and RT-PCR to examine the activation of IRP and the expression of IRP 2 mRNA onaspirin induced ferritin formation. RESULTS: Aspirin at low concentration (0.1mmol/L) induced significant increase in ferritin expression in a concentration-dependent fashion up to 25% over basal levels. Aspirin induced cytoprotection from H 2O 2 damage increased significantly following ferritin formation in endothelial cells.However, in the presence of iron chelator desferrioxamine, aspirin enhanced ferritin synthesis was abrogated with a 3 fold increase in the activity of IRP and significant increase in IRP 2 mRNA level. In contrast, FeCl 3 and aspirin both increased the level of induced ferritin synthesis with significant decrease in IRP activity and IRP 2 mRNA level. CONCLUSION: The effect of aspirin induced ferritin synthesis on resistance to oxidative damage in endothelium was operated through down-regulating IRP activation and IRP 2 mRNA level.