Ubiquitin proteasomal system is a potential target of the toxic effects of organophosphorus flame retardant triphenyl phosphate

The consumption of the widely used flame retardant Triphenyl phosphate (TPP) is increasing. It is now frequently detected in the environment and also domestically. Although the possibility of dermal exposure to TPP is quite high, little is known about its potential molecular toxicity mechanisms. In this study, we found that TPP caused cytotoxicity on human skin keratinocytes (HaCaT) and significantly inhibited the proliferation and cell migration in a concentration-dependent manner. Additionally, HaCaT cells were sensitive to TPP-induced apoptosis. Reactive oxygen species production was induced with TPP, which increased the protein carbonyla-tion and lipid peroxidation levels. Moreover, TPP inhibited proteasome activity and increased the accumulation of ubiquitinated proteins. Exposure to TPP significantly increased the HSP90, HSP70, GRP94 and GRP78 protein levels. Overall, our findings indicate that TPP may pose a risk to human health and contribute to the current understanding of the risks of TPP at the molecular level.

Automated summary

The widely used flame retardant Triphenyl phosphate (TPP) has been found to be cytotoxic to human skin keratinocytes, inhibiting cell proliferation and migration, and inducing apoptosis. TPP also induces the production of reactive oxygen species, increases protein oxidation and lipid peroxidation, and affects protein degradation and ubiquitination processes.