Perfluorooctanoic acid induces hepatocellular endoplasmic reticulum stress and mitochondrial-mediated apoptosis in vitro via endoplasmic reticulum-mitochondria communication

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant that is widely distributed in the natural environment. Cohort study showed that PFOA-producing workers displayed a significant increase for mortality of liver cancer and liver cirrhosis. However, the underlying mechanism of PFOA-induced hepatotoxicity is far from clear. In this research, cell viability, apoptosis rate, reactive oxygen species, mitochondrial membrane potential (Delta psi m), calcium ion levels, and protein expressions of human liver L02 cells in response to PFOA were determined. Results indicated that a 24 h-treatment with 64 and 256 mu M PFOA could remarkably induce mitochondrial-mediated apoptosis via initiating the vicious cycle between endoplasmic reticulum stress and oxidative stress, thereby increasing the level of calcium ion and decreasing the level of Delta psi m, simultaneously elevating the protein expressions of Cyclophilin D (CYPD), Bcl-2 homologous antagonist/killer (Bak), Bcl-2associated X protein (Bax), Bcl-2-like protein 11 (Bim), cytochrome C (Cyt-C), 78 kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and thioredoxininteracting protein (TXNIP), while inhibiting the protein expression of tumor necrosis factor receptorassociated protein 1 (TRAP1), Lon protease 1 (Lonp1), Pro-caspase-9, B-cell lymphoma-2 (Bcl-2), and Sigma 1-type opioid receptor (Sig-1R) (p < 0.05). To sum up, PFOA-induced hepatocellular endoplasmic reticulum stress and mitochondrial-mediated apoptosis in vitro was regulated by endoplasmic reticulum (ER)-mitochondria communication via mitochondria-associated ER membranes (MAMs).

Automated summary

PFOA induces mitochondrial-mediated apoptosis in liver cells, which is regulated by communication between the endoplasmic reticulum and mitochondria.