Research for heart failure by regulating myocardial energy metabolism with p53 and TIGAR.

我们证明，p53和TIGAR抑制糖酵解在缺氧的心肌细胞和糖酵解的抑制密切参与细胞凋亡，表明p53和TIGAR是重要的介质的细胞能量稳态和细胞死亡缺血应激。(Am J Physiol Heart Circ Physiol 299：H1908.H1916，2010.）我们还发现，p53/TIGAR介导的心肌细胞线粒体自噬的抑制是负责线粒体完整性和随后的细胞凋亡，这一过程是密切参与p53介导的心肌梗死后心室重构的损害。（J Mol Cell Cardiol.; 52：175-184，2012）控制p53/TIGAR信号的方法对于开发心力衰竭的新疗法是重要的。

We demonstrated that p53 and TIGAR inhibit glycolysis in hypoxic myocytes and that inhibition of glycolysis is closely involved in apoptosis, suggesting that p53 and TIGAR are significant mediators of cellular energy homeostasis and cell death under ischemic stress.(Am J Physiol Heart Circ Physiol 299 : H1908.H1916, 2010.) We also found that p53/TIGAR-mediated inhibition of myocyte mitophagy is responsible for impairment of mitochondrial integrity and subsequent apoptosis, the process of which is closely involved in p53-mediated ventricular remodeling after myocardial infarction.(J Mol Cell Cardiol.; 52 : 175-184, 2012) Approache to control p53/TIGAR signal is important to develop novel therapeutics for heart failure.