Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARα) by perfluoroalkyl acids (PFAAs): Further investigation of C4-C12 compounds

Perfluorinated alkyl acids (PFAAs) are manufactured surfactants found globally in the environment and in tissues of humans and wildlife. Several PFAAs adversely affect rodents and activation of PPAR alpha is thought to be their mode of action. Our previous study demonstrated that some PFAAs activate mouse and human PPAR alpha in transiently transfected COS-1 cells. Here, we test more PFAAs for PPAR alpha activation in the same system. Cells were transfected with either mouse or human PPAR alpha-luciferase reporter plasmid, exposed the next day to either vehicle, PPAR alpha agonist (WY14643), perfluoropentanoic acid (C5), perfluoroheptanoic acid (C7), perfluorooctanoic acid (C8), perfluoroundecanoic acid (C11), or perfluorododecanoic acid (C12) at concentrations from 0.5 mu M to 100 mu M, and luminescence was measured after 24 h. C8 induced the highest activity for human PPAR alpha, followed by C7, C5, and C11. C12 had little activity. C8 induced the highest activity for mouse PPAR alpha, followed by C11, C7, C12 and C5. The two studies together found increasing activity of PPAR alpha with increasing chain length of the PFAA up to perfluorononanoic acid (C9) and lower activity with longer chain PFAAs with both mouse and human PPAR alpha. Published by Elsevier Inc.