Triacylglycerol-induced impairment in mitochondrial biogenesis and function in J774.2 and mouse peritoneal macrophage foam cells.
The aim of this study was to detect mitochondrial alterations in J774.2 macrophages and mouse peritoneal macrophages (MPM) foam cells. J774.2 and MPM cells were exposed to triacylglycerol (TG) emulsion (1 mg/ml) for induction of fat accumulation. Impairment of mitochondrial function was reflected by reduced cellular ATP production and decreased expression of subunits of mitochondrial complexes I and III. The expression of subunit IV of complex IV remained unchanged, however, the content of its precursor in cells increased. Inhibitors of mitochondrial complexes, rotenone (0.1 microM) and myxothiazol (25 nM), protected the viability in TG-loaded macrophages. The exposure to TG caused downregulation of PPARgamma coactivator (PGC)-1alpha and nuclear respiratory factor (NRF)-1. Activation of peroxisome proliferator-activated receptors attenuated reactive oxygen species production in the foam cells. Treatment with antioxidant N-acetylcysteine (NAC) prevented lipid-mediated mitochondrial and cellular damage. In conclusion, this study demonstrates the important role of mitochondrial biogenesis dysfunction in TG-induced lipotoxicity in macrophages.
Aronis
Anna
A
School of Nutritional Sciences, Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Aharoni-Simon
Michal
M
Madar
Zecharia
Z
Tirosh
Oren
O
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation / Q000502:physiology; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D051266:Nuclear Respiratory Factor 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity; D013025:Glycine max; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014280:Triglycerides / Q000633:toxicity*
D004272:DNA, Mitochondrial; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D014280:Triglycerides; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1