心房颤动患者心房组织AMPK/PGC-1a通路表达改变的研究

目的 探讨心房颤动（房颤）患者心房肌组织中AMPK/PGC-1α信号通路表达是否改变,探究该通路在在房颤过程中的作用。方法 选择2018年12月至2019年11月在我科行心脏手术的患者76例,根据术前24 h动态心电图及病史分为房颤组（AF,41例）和窦性组（SR,35例）,术中切除左心耳组织留存。使用蛋白质印迹法（western blot,WB）检测心耳组织中AMPK、PGC-1α、NRF1、TFAM的表达量水平。免疫组织化学染色定量左心耳组织TFAM水平。Logistic回归分析AMPK、PGC-1α、NRF1、TFAM的表达水平与术后早期房颤之间的关系。结果 WB结果显示,与窦性心率患者相比,房颤患者左心耳组织内的AMPK、PGC-1α、NRF1、TFAM的表达明显降低（AMPK: 0.75±0.27 VS 0.47±0.43, PGC-1α:0.55±0.10 VS 0.35±0.10, NRF1:0.67±0.11 VS 0.46±0.15, TFAM:0.88±0.19 VS 0.58±0.30,P均<0.05）。免疫组化结果显示房颤患者的左心耳TFAM水平较窦性患者明显降低（8.86±2.13 VS 5.95±2.53, P<0.05）。Logistic回归分析显示TFAM为术后早期房颤的影响因素（b=-0.55, P<0.05）补充数据,低水平TFAM会增加术后新发房颤的风险。结论 AMPK/PGC-1α信号通路参与了房颤过程,其表达在房颤心患者房内降低。TFAM为术后早期房颤的相关因素,低水平TFAM会增加术后发生房颤的风险。     

Bisphenol-A inhibits mitochondrial biogenesis via impairment of GFER mediated mitochondrial protein import in the rat brain hippocampus

Mitochondrial biogenesis relies on different protein import machinery, as mitochondrial proteins are imported from the cytosol. The mitochondrial intermembrane space assembly (MIA) pathway consists of GFER/ALR and CHCHD4/Mia40, responsible for importing proteins and their oxidative folding inside the mitochondria. The MIA pathway plays an essential role in complex IV (COX IV) biogenesis via importing copper chaperone COX17, associated with the respiratory chain. BPA, an environmental toxicant, found in consumable plastics, causes neurotoxicity via impairment in mitochondrial dynamics, neurogenesis, and cognitive functions. We studied the levels of key regulatory proteins of mitochondrial import pathways and mitochondrial biogenesis after BPA exposure in the rat hippocampus. BPA caused a significant reduction in the levels of mitochondrial biogenesis proteins (PGC1α, and TFAM) and mitochondrial import protein (GFER). Immunohistochemical analysis showed reduced co-localization of NeuN with GFER, PGC-1α, and TFAM suggesting impaired mitochondrial biogenesis and protein import. BPA exposure resulted in damaged mitochondria with distorted cristae in neurons and caused a significant reduction in GFER localization inside IMS as depicted by immunogold electron microscopy. The reduced levels of GFER resulted in defective COX17 import. The translocation of cytochrome c into the cytosol and increased cleaved caspase-3 levels triggered apoptosis due to BPA toxicity. Overall, our study implicates GFER as a potential target for impaired mitochondrial protein machinery, biogenesis, and apoptosis against BPA neurotoxicity in the rat hippocampus.     

线粒体DNA的转录机制

真核生物的基因由核基因和线粒体基因(mtDNA)共同组成,mtDNA的生物合成是一个非常复杂的过程,需要核基因和mtDNA共同协同调节完成,大多线粒体蛋白在由核基因编码好后经特殊通道输送到线粒体内参与线粒体的各项生物合成.线粒体DNA转录需要核基因编码的几种蛋白,包括一个线粒体RNA聚合酶(POLRMT),线粒体转录因子A(TFAM),线粒体转录因子B1(TFB1M)或者线粒体转录因子B2(TFB2M)两者之一.本文对哺乳动物线粒体转录各因子的功能、 各因子间的相互作用以及线粒体转录的调节进行了综述.