Silencing of lipocalin-2 improves cardiomyocyte viability under iron overload conditions via decreasing mitochondrial dysfunction and apoptosis.

This study aimed to investigate the mechanistic roles of LCN-2 and LCN-2 receptors (LCN-2R) as iron transporters in cardiomyocytes under iron overload condition. H9c2 cardiomyocytes were treated with either LCN-2 small interfering RNA (siRNA) or LCN-2R siRNA or L-type or T-type calcium channel (LTCC or TTCC) blockers, or iron chelator deferiprone (DFP). After the treatments, the cells were exposed to Fe or Fe , after that biological parameters were determined. Silencing of lipocalin-2 or its receptor improved cardiomyocyte viability via decreasing iron uptake, mitochondrial fission, mitophagy and cleaved caspase-3 only in the Fe overload condition. In contrast, treatments with LTCC blocker and TTCC blocker showed beneficial effects on those parameters only in conditions of Fe overload. Treatment with DFP has been shown beneficial effects both in Fe and Fe overload condition. All of these findings suggested that LTCC and TTCC play crucial roles in the Fe uptake, whereas LCN-2 and LCN-2R were essential for Fe uptake into the cardiomyocytes under iron overload conditions.