The endocrine disruptor mono-(2-ethylhexyl) phthalate affects the differentiation of human liposarcoma cells (SW 872).
Esters of phthalic acid (phthalates) are largely used in industrial plastics, medical devices, and pharmaceutical formulations. They are easily released from plastics into the environment and can be found in measurable levels in human fluids. Phthalates are agonists for peroxisome proliferator-activated receptors (PPARs), through which they regulate translocator protein (TSPO; 18 kDa) transcription in a tissue-specific manner. TSPO is a drug- and cholesterol-binding protein involved in mitochondrial respiration, steroid formation, and cell proliferation. TSPO has been shown to increase during differentiation and decrease during maturation in mouse adipocytes. The purpose of this study was to establish the effect of mono-(2-ethylhexyl) phthalate (MEHP) on the differentiation of human SW 872 preadipocyte cells, and examine the role of TSPO in the process. After 4 days of treatment with 10 µM MEHP, we observed changes in the transcription of acetyl-CoA carboxylase alpha, adenosine triphosphate citrate lyase, glucose transporters 1 and 4, and the S100 calcium binding protein B, all of which are markers of preadipocyte differentiation. These observed gene expression changes coincided with a decrease in cellular proliferation without affecting cellular triglyceride content. Taken together, these data suggest that MEHP exerts a differentiating effect on human preadipocytes. Interestingly, MEHP was able to temporarily increase TSPO mRNA levels through the PPAR-α and β/δ pathways. These results suggest that TSPO can be considered an important player in the differentiation process itself, or alternatively a factor whose presence is essential for adipocyte development.
Research Institute of the McGill University Health Center and the Departments of Medicine, Biochemistry, and Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Enrico
E
Campioli
Amani
A
Batarseh
Jiehan
J
Li
Vassilios
V
Papadopoulos
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000494:pharmacology; D052244:Endocrine Disruptors / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008080:Liposarcoma / Q000473:pathology*; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics; D051744:Protein Kinase C-epsilon / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000172:deficiency / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D015415:Biomarkers; D052244:Endocrine Disruptors; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D018079:Receptors, GABA; C499229:TSPO protein, human; D004051:Diethylhexyl Phthalate; D051744:Protein Kinase C-epsilon; C016599:mono-(2-ethylhexyl)phthalate; D001973:Bromodeoxyuridine; D013755:Tetradecanoylphorbol Acetate