Cardiomyocyte Pdk4 response is associated with metabolic maladaptation in aging.
Cardiomyocyte Pdk4 response is associated with metabolic maladaptation in aging.
复制标题
心肌细胞PDK4反应与衰老中的代谢不良有关。
作者：
缺血性心脏病（IHD）是死亡的主要原因，年龄范围是发展的主要因素。衰老增加对缺血性损伤的脆弱性的机制还不清楚。我们的目标是使用单细胞RNA测序来发现老年小鼠和年轻小鼠之间各种细胞类型的转录差异，这可能导致与年龄相关的缺血损伤脆弱性。利用10× Genomics单细胞RNA测序，我们能够完成生物信息学分析，以识别新的差异基因表达。在我们收集的样品的分析中，我们检测到丙酮酸脱氢酶激酶4（Pdk 4）的表达显著差异表达。特别是在心肌细胞群体中，发现在缺血/再灌注条件下，与老年小鼠相比，年轻小鼠群体中的Pdk 4显着上调。pdk 4负责抑制丙酮酸脱氢酶，导致葡萄糖代谢的调节。由于老年心肌细胞中Pdk 4表达减少，可能对葡萄糖氧化能量的依赖性增加。通过生化代谢组学分析，观察到年轻心脏中丙酮酸的丰度高于老年心脏，表明糖酵解活性较低。我们认为Pdk 4反应提供了有价值的见解机制，使年轻的心脏更有效地处理缺血性损伤应力比老年心脏。心肌细胞Pdk 4调节丙酮酸脱氢酶在衰老中对缺血性应激的反应受损。
Ischemic heart disease (IHD) is the leading cause of death, with age range being the primary factor for development. The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. We aim to use single‐cell RNA sequencing to discover transcriptional differences in various cell types between aged and young mice, which may contribute to aged‐related vulnerability to ischemic insult. Utilizing 10× Genomics Single‐Cell RNA sequencing, we were able to complete bioinformatic analysis to identity novel differential gene expression. During the analysis of our collected samples, we detected Pyruvate Dehydrogenase Kinase 4 (Pdk4) expression to be remarkably differentially expressed. Particularly in cardiomyocyte cell populations, Pdk4 was found to be significantly upregulated in the young mouse population compared to the aged mice under ischemic/reperfusion conditions. Pdk4 is responsible for inhibiting the enzyme pyruvate dehydrogenase, resulting in the regulation of glucose metabolism. Due to decreased Pdk4 expression in aged cardiomyocytes, there may be an increased reliance on glucose oxidization for energy. Through biochemical metabolomics analysis, it was observed that there is a greater abundance of pyruvate in young hearts in contrast to their aged counterparts, indicating less glycolytic activity. We believe that Pdk4 response provides valuable insight towards mechanisms that allow for the young heart to handle ischemic insult stress more effectively than the aged heart. Cardiomyocyte Pdk4 modulating pyruvate dehydrogenase is impaired in response to ischemic stress in aging.
登录
查看更多内容
影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
3.6
作者：
Jiang M;Xie X;Cao F;Wang Y
通讯作者：
Wang Y
影响因子：
20.1
作者：
Liu LX;Rowe GC;Yang S;Li J;Damilano F;Chan MC;Lu W;Jang C;Wada S;Morley M;Hesse M;Fleischmann BK;Rabinowitz JD;Das S;Rosenzweig A;Arany Z
通讯作者：
Arany Z
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
20.1
作者：
Ren D;Fedorova J;Davitt K;Van Le TN;Griffin JH;Liaw PC;Esmon CT;Rezaie AR;Li J
通讯作者：
Li J