Nencki Institute of Experimental Biology PAS, Warsaw, Poland.
Int J Biochem Cell Biol. 2012 Sep;44(9):1390-7. doi: 10.1016/j.biocel.2012.05.022. Epub 2012 Jun 9.
Mitochondrial response of EA.hy926 endothelial cells to tumour necrosis factor alpha (TNFα) was investigated. It was confirmed that TNFα stimulates reactive oxygen species (ROS) generation and increases intercellular adhesion molecule-1 (ICAM-1) level. These changes were paralleled by elevated oxygen consumption, slightly raised total mitochondrial mass and increased manganese superoxide dismutase (Mn-SOD) and uncoupling protein 2 (UCP2) content. They also correlated with a rise of mitochondrial transcription factor 1 (TFAM), nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, which are involved in regulation of mitochondrial biogenesis and an elevated level of selected respiratory chain proteins. Thus, the apparent stimulatory effect of TNFα on mitochondrial metabolism probably reflects an increased amount of mitochondria rather than activation of biochemical processes per se, although the latter cannot be excluded definitely. These observations are similar to those described for cardiac muscle cells challenged with bacterial lipopolysaccharide (LPS), in which mitochondrial biogenesis was postulated. Stimulation of mitochondrial biogenesis could be a mechanism activated to prevent TNFα-induced cell death.
研究了肿瘤坏死因子 α（TNFα）对 EA.hy926 内皮细胞线粒体的反应。研究证实，TNFα 刺激活性氧（ROS）的产生，并增加细胞间黏附分子-1（ICAM-1）的水平。这些变化伴随着耗氧量的增加、线粒体总质量的轻微升高、锰超氧化物歧化酶（Mn-SOD）和解偶联蛋白 2（UCP2）含量的增加。它们还与线粒体转录因子 1（TFAM）、核呼吸因子 1（NRF-1）和过氧化物酶体增殖物激活受体-γ共激活因子 1α（PGC-1α）的升高相关，这些因子参与调节线粒体生物发生和选定呼吸链蛋白的水平。因此，TNFα 对线粒体代谢的明显刺激作用可能反映了线粒体数量的增加，而不是生化过程本身的激活，尽管不能完全排除后者。这些观察结果与用细菌脂多糖（LPS）刺激心肌细胞所描述的情况相似，在这种情况下，线粒体生物发生被假定存在。刺激线粒体生物发生可能是一种被激活的机制，以防止 TNFα 诱导的细胞死亡。
