Polybrominated diphenyl ethers (PBDEs), a kind of flame retardants, were widely used in the furniture, textile and electronics industries. Because of their lipophilic, persistent and bio-accumulative properties, PBDEs were listed on the Stockholm Convention as typical persistent organic pollutants (POPs). We have previously reported that a highly active, quinone-type metabolite of PBDEs (PBDEQ) causes DNA damage and subsequently triggers apoptosis. However, it is remaining unclear whether PBDEQ provokes protein damage and stimulates corresponding signaling cascade. Using human normal liver (LO2) cells as an in vitro model, we demonstrated that PBDEQ causes oxidative protein damage through excess reactive oxygen species (ROS). Consistently, we found PBDEQ exposure causes the depletion of protein thiol group, the appearance of carbonyl group and the accumulation of protein aggregates. Endoplasmic reticulum (ER) stress was involved in the repair of oxidized proteins. Under the scenario of severe damage, LO2 cells degrade oxidized proteins through ubiquitin-proteasome system (UPS) and autophagy. The blockage of these protein degradation pathways aggravates PBDEQ-induced cytotoxicity in LO2 cells, whilst antioxidant N-acetyl-cysteine (NAC) rescues PBDEQ-induced oxidative protein damage conversely. In summary, our current study first demonstrated PBDEQ-induced protein oxidative damage in LO2 cells, which offer a better understanding of the cytotoxicity of PBDEs and corresponding metabolites.

多溴联苯醚（PBDEs）是一种阻燃剂，已广泛用于家具，纺织和电子行业。由于多溴二苯醚具有亲脂性，持久性和生物蓄积性，因此在《斯德哥尔摩公约》中被列为典型的持久性有机污染物（POPs）。我们以前曾报道过，PBDEs（PBDEQ）的高活性醌型代谢物会引起DNA损伤，并随后引发细胞凋亡。但是，尚不清楚PBDEQ是否引起蛋白质损伤并刺激相应的信号级联反应。使用人类正常肝（LO2）细胞作为体外在模型中，我们证明了PBDEQ通过过量的活性氧（ROS）引起氧化蛋白损伤。一致地，我们发现PBDEQ暴露会导致蛋白质硫醇基的消耗，羰基的出现以及蛋白质聚集体的积累。内质网（ER）应力参与氧化蛋白的修复。在严重破坏的情况下，LO2细胞通过泛素-蛋白酶体系统（UPS）和自噬降解氧化蛋白。这些蛋白质降解途径的阻滞加重了PBDEQ诱导的LO2细胞的细胞毒性，而抗氧化剂N-乙酰半胱氨酸（NAC）反过来挽救了PBDEQ诱导的氧化蛋白损伤。总而言之，我们目前的研究首次证明了PBDEQ诱导的LO2细胞中蛋白质的氧化损伤，