@article{ref1,
title="Toxicity of the flame-retardant BDE-49 on brain mitochondria and neurons enhanced by a PTEN-deficient background",
journal="Toxicological sciences",
year="2013",
author="Napoli, Eleonora and Hung, Connie and Wong, Sarah and Giulivi, Cecilia",
volume="132",
number="1",
pages="196-210",
abstract="Polybrominated diphenyl ethers (PBDEs) represent an important group of flame-retardants extensively used, which tonnage in the environment has been steadily increasing over the past 25 years. PBDEs or metabolites can induce neurotoxicity and mitochondrial dysfunction (MD) through a variety of mechanisms. Recently, PBDEs with <5 Br substitutions (i.e., BDE-47 and BDE-49) had gained interest because of their high bioaccumulation. In particular, congeners such as BDE-49 arise as one of the most biologically active with concentrations typically lower than those observed for BDE-47 in biological tissues; however, its potential to cause MD at biologically relevant concentrations is unknown. To this end, the effect of BDE-49 was studied in brain mitochondria and neuronal progenitor striatal cells (NPC). BDE-49 uncoupled mitochondria at concentrations <0.1 nM, whereas at <1 nM inhibited the electron transport at Complex V (mixed type inhibition; IC50 = 6 nM) and Complex IV (noncompetitive inhibition; IC50 = 40 nM). These concentrations are easily achieved in plasma concentrations considering that BDE-49 (this study, 400-fold) and other PBDEs accumulate 1-3 orders of magnitude in the cells, particularly in mitochondria and microsomes. Similar effects were observed in NPC, and exacerbated with PTEN (negative modulator of the PI3K/Akt pathway) deficiency, background associated with autism-like behavior, schizophrenia and epilepsy. PBDE-mediated MD per se or enhanced by a background that confers susceptibility to this exposure, may have profound implications in the energy balance of brain.<p /> <p>Language: en</p>",
language="en",
issn="1096-6080",
doi="10.1093/toxsci/kfs339",
url="http://dx.doi.org/10.1093/toxsci/kfs339"
}