Transcriptomic and metabolomic analysis identifies potential targets of HADHA lactylation in LPS-treated H9c2 cells

Serum lactate levels are used to evaluate tissue hypoxia and predict outcomes in cases of sepsis and septic shock. Lactate can participate in a posttranslational modification known as lactylation, but its role in sepsis-induced myocardial depression remains unclear. H9c2 cells were transfected with plasmids with flag-tagged trifunctional enzyme subunit alpha (HADHA, Flag-HADHA) or HADHA mutated at sites 166 and 728 (Flag-HADHAK166R/K728R). After LPS treatment, the transcriptomic and metabolomic analyses were performed with the transfected H9c2 cells. The differentially expressed genes (DEGs) from transcriptomic analysis and differential metabolites from metabolomic analysis were obtained. These DEGs and differential metabolites may help reveal a role for HADHA in sepsis-induced myocardial depression.

血清乳酸水平（serum lactate levels）可用于评估组织缺氧（tissue hypoxia），并预测败血症（sepsis）及脓毒性休克（septic shock）患者的预后。乳酸可参与一种名为乳酸化修饰（lactylation）的翻译后修饰（posttranslational modification）过程，但其在脓毒症诱导的心肌抑制（sepsis-induced myocardial depression）中所发挥的作用仍不明确。本研究将携带flag标签的三功能酶亚基α（trifunctional enzyme subunit alpha，缩写为HADHA，即Flag-HADHA），以及166与728位点发生突变的HADHA（Flag-HADHAK166R/K728R）的质粒转染至H9c2细胞中。经脂多糖（lipopolysaccharide，LPS）处理后，对转染后的H9c2细胞开展转录组学与代谢组学分析（transcriptomic and metabolomic analyses），获取转录组学分析得到的差异表达基因（differentially expressed genes，DEGs）以及代谢组学分析得到的差异代谢物（differential metabolites）。上述差异表达基因与差异代谢物或有助于揭示HADHA在脓毒症诱导的心肌抑制中的作用。