Perfluorooctanoic acid activates the unfolded protein response in pancreatic acinar cells

Perfluoroalkyl substances, such as perfluorooctanoic acid (PFOA), are widely used in consumer and industrial applications. Human epidemiologic and animal studies suggest that PFOA exposure elicits adverse effects on the pancreas; however, little is known about the biological effects of PFOA in this...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2020-11, Vol.34 (11), p.e22561-n/a
Main Authors: Hocevar, Sarah E., Kamendulis, Lisa M., Hocevar, Barbara A.
Format: Article
Language:English
Subjects:
Acinar cells
Activating transcription factor 6
Antioxidants
Biological effects
Calcium ions
Endonuclease
Endoplasmic reticulum
Epidemiology
ER stress
Industrial applications
Inositol 1,4,5-trisphosphate receptors
Kinases
Oxidative stress
Pancreas
pancreatic acinar cell
Perfluoro compounds
Perfluoroalkyl & polyfluoroalkyl substances
Perfluorooctanoic acid
PFOA
Pretreatment
Protein folding
Protein kinase
Proteins
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Summary:Perfluoroalkyl substances, such as perfluorooctanoic acid (PFOA), are widely used in consumer and industrial applications. Human epidemiologic and animal studies suggest that PFOA exposure elicits adverse effects on the pancreas; however, little is known about the biological effects of PFOA in this organ. In this study, we show that PFOA treatment of mouse pancreatic acinar cells results in endoplasmic reticulum (ER) stress and activation of the protein kinase‐like endoplasmic reticulum kinase (PERK), inositol‐requiring kinase/endonuclease 1α (IRE1α), and activating transcription factor 6 arms of the unfolded protein response (UPR) pathway. PFOA‐stimulated activation of the UPR was blocked by pretreatment with specific PERK and IRE1α inhibitors and the chemical chaperone 4‐phenyl butyrate, but not the antioxidants N‐acetyl‐ l‐cysteine and Tiron. PFOA treatment led to increased cytosolic Ca+2 levels and induction of the UPR was blocked by an inhibitor of the inositol 1,4,5‐trisphosphate receptor. These findings indicate that PFOA‐induced ER stress may be the mechanistic trigger leading to oxidative stress in the pancreas.
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.22561