Firemaster® 550 and its components isopropylated triphenyl phosphate and triphenyl phosphate enhance adipogenesis and transcriptional activity of peroxisome proliferator activated receptor (Pparγ) on the adipocyte protein 2 (aP2) promoter

Autor: Shaimaa Ahmed, Ella Atlas, Emily W. Y. Tung, Vian Peshdary
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Physiology
Protein Expression
Peroxisome proliferator-activated receptor
lcsh:Medicine
Gene Expression
010501 environmental sciences
01 natural sciences
Biochemistry
Mice
Endocrinology
Animal Cells
Gene expression
Adipocytes
Medicine and Health Sciences
Insulin
Receptor
lcsh:Science
Promoter Regions
Genetic
Connective Tissue Cells
chemistry.chemical_classification
Multidisciplinary
Adipogenesis
biology
Chemistry
Cell Differentiation
Lipids
Organophosphates
Cell biology
Physiological Parameters
Connective Tissue
medicine.symptom
Cellular Types
Anatomy
Research Article
Transcriptional Activation
Polybrominated Biphenyls
Research and Analysis Methods
Fatty Acid-Binding Proteins
03 medical and health sciences
3T3-L1 Cells
DNA-binding proteins
medicine
Genetics
Gene Expression and Vector Techniques
Adipocyte Differentiation
Animals
Gene Regulation
Obesity
adipocyte protein 2
Enhancer
Molecular Biology Techniques
Transcription factor
Molecular Biology
0105 earth and related environmental sciences
Diabetic Endocrinology
Molecular Biology Assays and Analysis Techniques
Dose-Response Relationship
Drug
lcsh:R
Body Weight
Biology and Life Sciences
Proteins
Cell Biology
Hormones
Regulatory Proteins
PPAR gamma
030104 developmental biology
Biological Tissue
Mechanism of action
biology.protein
lcsh:Q
Transcription Factors
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 4, p e0175855 (2017)
ISSN: 1932-6203
Popis: Firemaster® 550 (FM550) is a chemical mixture currently used as an additive flame retardant in commercial products, and is comprised of 2-ethylhexyl-2,3,4,5-tertrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (IPTP). Animal and in vitro studies suggest that FM550, TPP and IPTP may have adipogenic effects and may exert these effects through PPARγ activation. Using murine 3T3-L1 preadipocytes, we investigated the detailed expression of transcription factors and adipogenic markers in response to FM550 and its components. Further we investigated the mechanism of action of the peroxisome proliferator-activated receptor gamma (PPARγ) on downstream targets of the receptor by focussing on the mature adipocyte marker, adipocyte protein 2 (aP2). In addition, we set to elucidate the components responsible for the adipogenic effects seen in the FM550 mixture. We show that FM550 and its components TPP, IPTP, and TBPH, but not TBB induced lipid accumulation in a dose-dependent manner. Interestingly, despite displaying enhanced lipid accumulation, TBPH did not alter the mRNA or protein expression of terminal differentiation markers. In contrast, FM550, TPP, and IPTP treatment enhanced lipid accumulation, and mRNA and protein expression of terminal differentiation markers. To further delineate the mechanisms of action of FM550 and its components we focussed on aP2 promoter activity. For this purpose we used the enhancer region of the mouse aP2 promoter using a 584-bp reporter construct containing an active PPRE located 5.4 kb away from the transcription start site of aP2. Exposure to FM550, IPTP, and TPP significantly increased PPARγ mediated aP2 enhancer activity. Furthermore, we show that TPP- and IPTP-dependent upregulation of aP2 was significantly inhibited by the selective PPARγ antagonist GW9662. In addition, chromatin immunoprecipitation experiments showed that IPTP and TPP treatment led to the recruitment of PPARγ to the regulatory region of aP2.
Databáze: OpenAIRE
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