PPAR-gamma Agonist GW1929 But Not Antagonist GW9662 Reduces TBBPA-Induced Neurotoxicity in Primary Neocortical Cells

摘要

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-gamma) 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 mu M TBBPA decreased the expression of PPAR-gamma 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-gamma protein expression. Thus, our data support neuroprotective potential of PPAR-gamma agonists. The PPAR-gamma antagonist GW9662 prevented the TBBPA-induced decrease in PPAR-gamma 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-gamma-dependent. Therefore, further studies of the mechanism of TBBPA action in the nervous system are needed.