PDK4型
糖尿病性心肌病
细胞凋亡
基因沉默
细胞生物学
流式细胞术
生物
下调和上调
分子生物学
内科学
心肌病
心力衰竭
医学
生物化学
基因
作者
Shumin Liang,Wenliang Tan,Huogeng Bao,Ziming Liu,Yuanyuan Liu,Lang Hong
出处
期刊:Current Molecular Medicine
[Bentham Science]
日期:2023-12-01
卷期号:23 (10): 1104-1115
被引量:1
标识
DOI:10.2174/1566524023666221021124202
摘要
Objectives: As a distinct type of cardiomyopathy, diabetic cardiomyopathy (DCM) is featured as diastolic or systolic cardiac dysfunction in diabetic patients. In order to broaden the understanding of molecular mechanisms in DCM, we intended to explore the mechanism of the interaction between PDK4 protein and Hmgcs2 in high glucose (HG)-induced myocardial damages. Methods: PDK4 and Hmgcs2 expression in the myocardium of diabetes mellitus (DM) model rats and HG-incubated cardiomyocyte line H9C2 was analyzed by western blot analysis. Echocardiography and TUNEL assay were utilized for respective assessment of cardiac structure and function and cardiomyocyte apoptosis in DM rats after silencing PDK4 or/and Hmgcs2. In vitro, the impact of PDK4 and Hmgcs2 on HG-induced cardiomyocyte injuries was identified with cell counting kit-8 and flow cytometry assays, along with detection of LDH release, caspase-3/7 activities, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Moreover, a coimmunoprecipitation assay was utilized to test the interaction between PDK4 and Hmgcs2. Results: Both PDK4 and Hmgcs2 were highly expressed in the myocardial tissues of DM rats. Mechanistically, PDK4 interacted with Hmgcs2 to upregulate Hmgcs2 expression in HG-induced H9C2 cells. Silencing PDK4 improved cardiac function and reduced cardiomyocyte apoptosis in DM rats. In HG-induced H9C2 cells, PDK4 or Hmgcs2 silencing enhanced cell viability and reduced LDH release, caspase-3/7 activities, cell apoptosis, and ROS and MDA levels, and these trends were further promoted by the simultaneous silencing of PDK4 and Hmgcs2. Conclusions: In summary, the silencing of PDK4 and Hmgcs2 alleviated HG-induced myocardial injuries through their interaction.
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