title: Molecular mechanisms of PFOA-induced toxicity in animals and humans: Implications for health risks.
abstract: As an emerging persistent organic pollutant (POP), perfluorooctanoate (PFOA) is one of the most abundant perfluorinated compounds (PFCs) in the environment. This review summarized the molecular mechanisms and signaling pathways of PFOA-induced toxicity in animals and humans as well as their implications for health risks in humans. Traditional PFOA-induced signal pathways such as peroxisome proliferating receptor alpha (PPARα), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), and pregnane-X receptor (PXR) may not be important for PFOA-induced health effects on humans. Instead, pathways including p53/mitochondrial pathway, nuclear lipid hyperaccumulation, phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT), and tumor necrosis factor-α/nuclear factor κB (TNF-α/NF-κB) may play an important role for PFOA-induced health risks in humans. Both in vivo and in vitro studies are needed to better understand the PFOA-induced toxicity mechanisms as well as the associated health risk in humans.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 210046, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Li
authors.affiliation: Soil and Water Science Department, University of Florida, Gainesville, FL 32611, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 210046, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 210046, China.
authors.forename: Xuxiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 210046, China. Electronic address: lizzycui@nju.edu.cn.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 210046, China; Soil and Water Science Department, University of Florida, Gainesville, FL 32611, United States. Electronic address: lqma@ufl.edu.
authors.forename: Lena Q
authors.initials: LQ
authors.lastname: Ma
mesh_terms: D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D000090702:Constitutive Androstane Receptor; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D047493:PPAR alpha / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002210:Caprylates; D000090702:Constitutive Androstane Receptor; D005466:Fluorocarbons; D047493:PPAR alpha; D019869:Phosphatidylinositol 3-Kinases; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C023036:perfluorooctanoic acid
keywords: Constitutive androstane receptor (CAR); Mitochondrial pathway; Nuclear lipid hyperaccumulation; Peroxisome proliferating receptor alpha (PPARα); Pregnane-X receptor (PXR); Tumor necrosis factor-α/nuclear factor κB (TNF-α/NF-κB)