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 Fe³⁺ or Fe²⁺ , 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 Fe³⁺ overload condition. In contrast, treatments with LTCC blocker and TTCC blocker showed beneficial effects on those parameters only in conditions of Fe²⁺ overload. Treatment with DFP has been shown beneficial effects both in Fe²⁺ and Fe³⁺ overload condition. All of these findings suggested that LTCC and TTCC play crucial roles in the Fe²⁺ uptake, whereas LCN-2 and LCN-2R were essential for Fe³⁺ uptake into the cardiomyocytes under iron overload conditions.