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Silencing of lipocalin‐2 improves cardiomyocyte viability under iron overload conditions via decreasing mitochondrial dysfunction and apoptosis
Author(s) -
Kumfu Sirinart,
SiriAngkul Natthaphat,
Chattipakorn Siriporn C.,
Chattipakorn Nipon
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30219
Subject(s) - deferiprone , gene silencing , mitochondrion , mitophagy , small interfering rna , apoptosis , viability assay , microbiology and biotechnology , receptor , chemistry , pharmacology , biology , deferoxamine , biochemistry , rna , gene , autophagy
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 3+ or Fe 2+ , 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 3+ overload condition. In contrast, treatments with LTCC blocker and TTCC blocker showed beneficial effects on those parameters only in conditions of Fe 2+ overload. Treatment with DFP has been shown beneficial effects both in Fe 2+ and Fe 3+ overload condition. All of these findings suggested that LTCC and TTCC play crucial roles in the Fe 2+ uptake, whereas LCN‐2 and LCN‐2R were essential for Fe 3+ uptake into the cardiomyocytes under iron overload conditions.