Endovascular hypothermia improves post-resuscitation myocardial dysfunction by increasing mitochondrial biogenesis in a pig model of cardiac arrest

The aim of the study was to investigate the effects of endovascular hypothermia on mitochondrial biogenesis in a pig model of prolonged cardiac arrest (CA). Ventricular fibrillation was electrically induced, and animals were left untreated for 10 min; then after 6min of cardiopulmonary resuscitation (CPR), defibrillation was attempted. 25 animals that were successfully resuscitated were randomized into three groups: Sham group (SG, 5, no CA), normal temperature group (NTG, 5 for 12 h observation and 5 for 24 h observation), and endovascular hypothermia group (EHG, 5 for 12 h observation and 5 for 24 h observation). The core temperatures (T_c) in the EHG were maintained at 34 ± 0.5 °C for 6 h by an endovascular hypothermia device (Coolgard 3000), then actively increased at the speed of 0.5 °C per hour during the next 6 h to achieve a normal body temperature, while T_c were maintained at 37.5 ± 0.5 °C in the NTG. Cardiac and mitochondrial functions, the quantification of myocardial mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, and NRF-2 were examined. Results showed that myocardial and mitochondrial injury and dysfunction increased significantly at 12 h and 24 h after CA. Endovascular hypothermia offered a method to rapidly achieve the target temperature and provide stable target temperature management (TTM). Cardiac outcomes were improved and myocardial injuries were alleviated with endovascular hypothermia. Compared with NTG, endovascular hypothermia significantly increased mitochondrial activity and biogenesis by amplifying mitochondrial biogenesis factors’ expressions, including PGC-1α, NRF-1, and NRF-2. In conclusions, endovascular hypothermia after CA alleviated myocardial and mitochondrial dysfunction, and was associated with increasing mitochondrial biogenesis.     

The PGC-1α-dependent pathway of mitochondrial biogenesis is upregulated in type I endometrial cancer

PGC-1α-dependent pathway of mitochondrial biogenesis was investigated for the first time in type I endometrial cancer and in normal endometrium. In cancer endometrial tissue the citrate synthase activity, the mitochondrial DNA content and the TFAM level were found doubled compared to control endometrial tissue. Moreover, a 1.6- and 1.8-fold increase, respectively, of NRF-1 and PGG-1α expression was found. This study demonstrates, for the first time, that the increased mitochondrial biogenesis in type I endometrial cancer is associated to the upregulation of PGC-1α signalling pathway.     

马来酸罗格列酮对人肺腺癌（A549）细胞中PGC-1α表达及增殖的影响

摘要：为探讨马来酸罗格列酮对肺腺癌（A549）细胞中PGC-1a表达和活性的影响,以及抑制细胞增殖的机制,我们首先构建了pGL3-PGC-1a promoter重组质粒,转染人肺腺癌A549细胞,用双荧光素酶报告基因系统检测马来酸罗格列酮对PGC-1a启动子转录活性的影响;实时定量PCR检测胞内PGC-1a mRNA的表达;用Mitotracker green染色, 流式细胞仪检测线粒体质量;细胞计数检测马来酸罗格列酮对A549细胞体外增殖的影响。结果显示,马来酸罗格列酮能够抑制pGL3-PGC-1apromoter重组质粒的转录活性,降低A549细胞PGC-1amRNA水平的表达及线粒体质量,具有明显的剂量依赖性（P<0.05）。其抑制PGC-1a表达和活性的IC50（约为80 umol/L）与马来酸罗格列酮抑制A549细胞增殖的IC50（约为80 umol/L）相符。结论 马来酸罗格列酮能够抑制A549细胞中PGC-1a的表达与活性,进而降低细胞中的线粒体质量。这有可能是罗格列酮抑制A549细胞增殖的原因之一。