title: PPAR-γ agonist GW1929 but not antagonist GW9662 reduces TBBPA-induced neurotoxicity in primary neocortical cells.
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.
authors.affiliation: Laboratory of Genomics and Biotechnology, Animal Sciences Faculty, University of Agriculture, Redzina 1B, 30-248, Krakow, Poland, anna.wojtowicz@ur.krakow.pl.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Wojtowicz
authors.forename: Konrad A
authors.initials: KA
authors.lastname: Szychowski
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kajta
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001577:Benzophenones; D002491:Central Nervous System Agents; D018696:Neuroprotective Agents; D047495:PPAR gamma; D011075:Polybrominated Biphenyls; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase; C505409:Casp3 protein, mouse; D053148:Caspase 3; C020806:tetrabromobisphenol A; C120099:GW 1929