Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related Potassium Channels

Title:Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related Potassium Channels

Volume: 24

Author(s): Huiqing Liang*, Huixian Li, Fangjiang Li, Xiaobo Xiong and Yang Gao

Affiliation:

• Department of Cardiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China

Abstract: 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 combined modulation of amiodarone and 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.

Cite this article as:

Liang Huiqing*, Li Huixian, Li Fangjiang, Xiong Xiaobo and Gao Yang, Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related Potassium Channels, Current Molecular Medicine 2024; 24 () . https://dx.doi.org/10.2174/0115665240265771231129105108