TNFα affects energy metabolism and stimulates biogenesis of mitochondria in EA.hy926 endothelial cells.
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.
Nencki Institute of Experimental Biology PAS, Warsaw, Poland.
Beata
B
Drabarek
Dorota
D
Dymkowska
Joanna
J
Szczepanowska
Krzysztof
K
Zabłocki
D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology*; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015415:Biomarkers; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013482:Superoxide Dismutase