PDF(Pubmed)
Abstract：
This study aims to elucidate the roles of Phosphoglycerate Mutase Family Member 5 (Pgam5) and Prohibitin 2 (Phb2) in the context of hyperglycemia-induced myocardial dysfunction, a critical aspect of diabetic cardiomyopathy. The research employed primary cardiomyocytes, which were then subjected to hyperglycemia treatment to mimic diabetic conditions. We used siRNA transfection to knock down Pgam5 and overexpressed Phb2 using adenovirus transfection to assess their individual and combined effects on cardiomyocyte health. Mitochondrial function was evaluated through measurements of mitochondrial membrane potential using the JC-1 probe, and levels of mitochondrial reactive oxygen species (ROS) were assessed. Additionally, the study involved qPCR analysis to quantify the transcriptional changes in genes related to mitochondrial fission and mitophagy. Our findings indicate that hyperglycemia significantly reduces cardiomyocyte viability and impairs mitochondrial function, as evidenced by decreased mitochondrial membrane potential and increased ROS levels. Pgam5 knockdown was observed to mitigate these adverse effects, preserving mitochondrial function and cardiomyocyte viability. On the molecular level, Pgam5 was found to regulate genes associated with mitochondrial fission (such as Drp1, Mff, and Fis1) and mitophagy (including Parkin, Bnip3, and Fundc1). Furthermore, overexpression of Phb2 countered the hyperglycemia-induced mitochondrial dysfunction and normalized the levels of key mitochondrial antioxidant enzymes. The combined data suggest a protective role for both Pgam5 knockdown and Phb2 overexpression against hyperglycemia-induced cellular and mitochondrial damage. The study elucidates the critical roles of Pgam5 and Phb2 in regulating mitochondrial dynamics in the setting of hyperglycemia-induced myocardial dysfunction. By modulating mitochondrial fission and mitophagy, Pgam5 and Phb2 emerge as key players in preserving mitochondrial integrity and cardiomyocyte health under diabetic conditions. These findings contribute significantly to our understanding of the molecular mechanisms underlying diabetic cardiomyopathy and suggest potential therapeutic targets for mitigating myocardial dysfunction in diabetes.
摘要：
本研究旨在阐明磷酸甘油酸变位酶家族成员5（Pgam5）和Prohibitin2（Phb2）在高血糖引起的心肌功能障碍中的作用。糖尿病性心肌病的一个关键方面。这项研究采用了原代心肌细胞，然后对其进行高血糖治疗以模拟糖尿病状况。我们使用siRNA转染敲低Pgam5和使用腺病毒转染过表达的Phb2来评估它们对心肌细胞健康的个体和组合影响。通过使用JC-1探针测量线粒体膜电位来评估线粒体功能，和线粒体活性氧（ROS）的水平进行了评估。此外,这项研究涉及qPCR分析，以量化与线粒体裂变和线粒体自噬相关的基因的转录变化。我们的研究结果表明，高血糖显著降低心肌细胞活力和损害线粒体功能，线粒体膜电位降低和ROS水平升高证明了这一点。观察到Pgam5敲低可以减轻这些不利影响，保留线粒体功能和心肌细胞活力。在分子水平上,Pgam5被发现调节与线粒体裂变相关的基因(如Drp1、Mff、和Fis1）和线粒体自噬（包括Parkin，Bnip3和Fundc1）。此外，Phb2的过表达对抗高血糖诱导的线粒体功能障碍，并使关键线粒体抗氧化酶的水平正常化。综合数据表明，Pgam5敲低和Phb2过表达对高血糖诱导的细胞和线粒体损伤均具有保护作用。该研究阐明了Pgam5和Phb2在高血糖引起的心肌功能障碍中调节线粒体动力学的关键作用。通过调节线粒体裂变和线粒体自噬，Pgam5和Phb2是糖尿病条件下保持线粒体完整性和心肌细胞健康的关键参与者。这些发现对我们了解糖尿病心肌病的分子机制有重要意义，并提出了减轻糖尿病心肌功能障碍的潜在治疗靶点。
