Iron induces protection and necrosis in cultured cardiomyocytes: Role of reactive oxygen species and nitric oxide
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We investigate here the role of reactive oxygen species and nitric oxide in iron-induced cardiomyocyte hypertrophy or cell death Cultured rat cardiomyocytes incubated with 20 mu M iron (added as FeCl3-Na nitrilotriacetate, Fe-NTA) displayed hypertrophy features that: included increased protein synthesis and cell size, plus realignment of F-actin filaments along with sarcomeres and activation of the atrial natriuretic factor acne promoter Incubation with higher Fe-NTA concentrations (100 mu M) produced cardiomyocyte death,by necrosis. Incubation for 24 h with Fe-NTA (20-40 mu M) or the nitric oxide donor Delta-nonoate increased iNOS mRNA but decreased iNOS protein levels: under these conditions. Lion stimulated the activity and the dimerization of iNOS. Fe-NTA (20 mu M) promoted short- and long-term generation of reactive oxygen species, whereas preincubation with L-arginine suppressed this response Preincubation with 20 mu M Fe-NTA also attenuated the necrotic cell death triggered by 100 mu M Fe-NTA, suggesting that these preincubation conditions have cardioprotective effects Inhibition of iNOS activity with 1400 W enhanced Iron-induced ROS generation and prevented both iron-dependent cardiomyocyte hypertrophy and cardioprotection In conclusion. we propose that Fe-NTA (20 mu M) stimulates iNOs activity and that the enhanced NO production, by promoting hypertrophy and enhancing survival mechanisms through ROS reduction, is beneficial to cardiomyocytes. At higher concentrations, however, iron triggers cardiomyocyte death by necrosis.