Abstract
Tetrabromobisphenol A (2,2-bis(4-hydroxy-3,5-dibromophenyl)propane; TBBPA) is a widely used brominated flame retardant. TBBPA induces neuronal damage, but the mechanism by which this occurs is largely unknown. We studied the possible involvement of peroxisome proliferator-activated receptor gamma (PPAR-γ) in TBBPA-induced apoptosis and toxicity in mouse primary neuronal cell cultures. TBBPA enhanced both, caspase-3 activity and lactate dehydrogenase (LDH) release in neocortical cells after 6 and 24 h of exposition. These data were supported at the cellular level with Hoechst 33342 staining. Immunoblot analyses showed that, compared with control cells, 10 μM TBBPA decreased the expression of PPAR-γ protein in neocortical neurons after 1–24 h of exposure. Co-treatment with TBBPA and GW1929 inhibited the TBBPA-induced caspase-3 activity, apoptotic body formation, and LDH release as well as TBBPA-induced decrease in PPAR-γ protein expression. Thus, our data support neuroprotective potential of PPAR-γ agonists. The PPAR-γ antagonist GW9662 prevented the TBBPA-induced decrease in PPAR-γ protein level, but it potentiated TBBPA-induced apoptotic and neurotoxic effects, which suggest that the mechanism of TBBPA action in neuronal cells is not only PPAR-γ-dependent. Therefore, further studies of the mechanism of TBBPA action in the nervous system are needed.
Highlights
Tetrabromobisphenol A (2,2-bis(4-hydroxy-3,5-dibromophenyl)propane; TBBPA) is a widely used brominated flame retardant (BFR)
We studied the possible involvement of peroxisome proliferator-activated receptor gamma (PPAR-c) in TBBPA-induced apoptosis and toxicity in mouse primary neuronal cell cultures
Kajta Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland e-mail: kajta@if-pan.krakow.pl and neurotoxic effects, which suggest that the mechanism of TBBPA action in neuronal cells is PPAR-c-dependent
Summary
Tetrabromobisphenol A (2,2-bis(4-hydroxy-3,5-dibromophenyl)propane; TBBPA) is a widely used brominated flame retardant (BFR). TBBPA can be utilized both as a reactive flame retardant in epoxy resin-printed circuit boards and as an additive flame retardant in a wide variety of commercial and household products, such as plastics, textiles and electronic appliances, including computers and televisions (Alaee et al 2003; Covaci et al 2009; de Wit et al 2010). This versatility has resulted in a dramatic increase in TBBPA production. Many studies indicate that rats and humans quickly metabolize TBBPA due to its rapid conjugation with glucuronic acid and elimination in the bile, TBBPA has been detected in cow and human milk, serum, adipose
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