Key result
Amiodarone promotes H9c2 cell apoptosis by restraining Sigmar1 expression and blocking KCNH2 potassium channels.
Why the study?
Heart failure is linked to mitochondria-mediated cardiomyocyte apoptosis, but the mechanism of amiodarone on cardiomyocyte mitochondrial toxicity was not fully understood.
Amiodarone induces cardiomyocyte apoptosis and mitochondrial toxicity by repressing Sigmar1 expression and blocking KCNH2-related potassium channels.
No immediate clinical implications; hypothesis-generating for Sigmar1 in amiodarone cardiotoxicity.
BACKGROUND: Heart failure (HF) is the ultimate transformation result of various cardiovascular diseases. Mitochondria-mediated cardiomyocyte apoptosis has been uncovered to be associated with this disorder. OBJECTIVE: This study mainly delves into the mechanism of the anti-arrhythmic drug amiodarone on mitochondrial toxicity of cardiomyocytes. METHODS: The viability of H9c2 cells treated with amiodarone at 0.5, 1, 2, 3, and 4 μM was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and Sigmar1 expression was examined by quantitative real-time PCR (qRTPCR). After transfection, the viability, apoptosis, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), and potassium voltage-gated channel subfamily H member 2 (KCNH2) expression in H9c2 cells were assessed by MTT, flow cytometry, ROS assay kit, mitochondria staining kit, and Western blot. RESULTS: Amiodarone at 1-4 μM notably weakened H9c2 cell viability with IC50 value of 2.62 ± 0.43 μM. Amiodarone at 0.5-4 μM also evidently suppressed the Sigmar1 level in H9c2 cells. Amiodarone repressed H9c2 cell viability and KCNH2 level and triggered apoptosis, ROS production and mitochondrial depolarization, while Sigmar1 upregulation reversed its effects. Moreover, KCNH2 silencing neutralized the effect of Sigmar1 up-regulation on H9c2 cell viability, apoptosis, and ROS production. CONCLUSION: Amiodarone facilitates the apoptosis of H9c2 cells by restraining Sigmar1 expression and blocking KCNH2-related potassium channels.
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Liang et al. (2024) studied Amiodarone-induced mitochondrial toxicity in cardiomyocytes. Amiodarone was evaluated on Cell viability, apoptosis, ROS level, mitochondrial membrane potential, and KCNH2 expression. Amiodarone facilitates the apoptosis of H9c2 cells by restraining Sigmar1 expression and blocking KCNH2-related potassium channels, with an IC50 for cell viability of 2.62 ± 0.43 μM.
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