Department of Cardiovascular Surgery, Affiliated 9th People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 201900, China.
Sci Rep. 2022 Jul 8;12(1):11684. doi: 10.1038/s41598-022-15743-0.
Heart failure (HF) is a global pandemic which affects about 26 million people. PFKM (Phosphofructokinase, Muscle), catalyzing the phosphorylation of fructose-6-phosphate, plays a very important role in cardiovascular diseases. However, the effect of PFKM in glycolysis and HF remains to be elucidated. H9c2 rat cardiomyocyte cells were treated with doxorubicin (DOX) to establish injury models, and the cell viability, apoptosis and glycolysis were measured. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting were used for gene expression. DOX treatment significantly inhibited PFKM expression in H9c2 cells. Overexpression of PFKM inhibited DOX-induced cell apoptosis and DOX-decreased glycolysis and oxidative phosphorylation (OXPHOS), while silencing PFKM promoted cell apoptosis and inhibited glycolysis and OXPHOS in H9c2 cells. Moreover, PFKM regulated DOX-mediated cell viability and apoptosis through glycolysis pathway. Mechanism study showed that histone deacetylase 1 (HDAC1) inhibited H3K27ac-induced transcription of PFKM in DOX-treated cells and regulated glycolysis. PFKM could inhibit DOX-induced cardiotoxicity by enhancing OXPHOS and glycolysis, which might benefit us in developing novel therapeutics for prevention or treatment of HF.
心力衰竭（HF）是一种全球性的大流行病，影响约 2600 万人。催化果糖-6-磷酸磷酸化的磷酸果糖激酶（PFKM）在心血管疾病中起着非常重要的作用。然而，PFKM 在糖酵解和 HF 中的作用仍有待阐明。用阿霉素（DOX）处理 H9c2 大鼠心肌细胞建立损伤模型，测量细胞活力、细胞凋亡和糖酵解。定量逆转录聚合酶链反应（RT-PCR）和免疫印迹用于基因表达。DOX 处理显著抑制 H9c2 细胞中 PFKM 的表达。PFKM 的过表达抑制 DOX 诱导的细胞凋亡和 DOX 降低的糖酵解和氧化磷酸化（OXPHOS），而沉默 PFKM 促进 H9c2 细胞中的细胞凋亡并抑制糖酵解和 OXPHOS。此外，PFKM 通过糖酵解途径调节 DOX 介导的细胞活力和细胞凋亡。机制研究表明，组蛋白去乙酰化酶 1（HDAC1）抑制了 DOX 处理细胞中 PFKM 的 H3K27ac 诱导转录，并调节了糖酵解。PFKM 可以通过增强 OXPHOS 和糖酵解来抑制 DOX 诱导的心脏毒性，这可能有助于我们开发预防或治疗 HF 的新疗法。
