Faculty of Medicine, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand.
Cardiac Electrophysiology Unit, Department of Physiology, Chiang Mai University, Chiang Mai, Thailand.
J Cell Physiol. 2021 Jul;236(7):5108-5120. doi: 10.1002/jcp.30219. Epub 2020 Dec 15.
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.
本研究旨在探讨铁过载条件下 LCN-2 和 LCN-2 受体（LCN-2R）作为心肌细胞中铁转运体的作用机制。用 LCN-2 小干扰 RNA（siRNA）或 LCN-2R siRNA 或 L 型或 T 型钙通道（LTCC 或 TTCC）阻滞剂或铁螯合剂地拉罗司（DFP）处理 H9c2 心肌细胞。处理后，细胞用 Fe 或 Fe 处理，然后测定生物学参数。只有在铁过载条件下，沉默脂联素-2 或其受体可通过减少铁摄取、线粒体裂变、线粒体自噬和裂解的 caspase-3 来提高心肌细胞活力。相比之下，LTCC 阻滞剂和 TTCC 阻滞剂的处理仅在 Fe 过载条件下对这些参数有有益的影响。DFP 的治疗在 Fe 和 Fe 过载条件下均显示出有益的效果。所有这些发现表明，LTCC 和 TTCC 在 Fe 摄取中起关键作用，而 LCN-2 和 LCN-2R 是铁过载条件下铁进入心肌细胞所必需的。
