Autophagy levels are elevated in barrett's esophagus and promote cell survival from acid and oxidative stress.

Autor: Kong J; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Whelan KA; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Laczkó D; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Dang B; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Caro Monroig A; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Soroush A; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Falcone J; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Amaravadi RK; Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.; Department of Medicine, and the Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania., Rustgi AK; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Ginsberg GG; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Falk GW; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Nakagawa H; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania., Lynch JP; Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania. lynchj@mail.med.upenn.edu.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2016 Nov; Vol. 55 (11), pp. 1526-1541. Date of Electronic Publication: 2015 Sep 16.
DOI: 10.1002/mc.22406
Abstrakt: Autophagy is a highly conserved mechanism that is activated during cellular stress. We hypothesized that autophagy may be induced by acid reflux, which causes injury, and inflammation, and therefore, contributes to the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Currently, the role of autophagy in BE and EAC is poorly studied. We quantitatively define autophagy levels in human BE cell lines, a transgenic mouse model of BE, and human BE, and EAC biopsies. Human non-dysplastic BE had the highest basal number of autophagic vesicles (AVs), while AVs were reduced in normal squamous cells and dysplastic BE cells, and nearly absent in EAC. To demonstrate a functional role for autophagy in BE pathogenesis, normal squamous (STR), non-dysplastic BE (CPA), dysplastic BE (CPD), and EAC (OE19) cell lines were exposed to an acid pulse (pH 3.5) followed by incubation in the presence or absence of chloroquine, an autophagy inhibitor. Acid exposure increased reactive oxygen species (ROS) levels in STR and CPA cells. Chloroquine alone had a small impact on intracellular ROS or cell survival. However, combination of chloroquine with the acid pulse resulted in a significant increase in ROS levels at 6 h in STR and CPA cells, and increased cell death in all cell lines. These findings establish increased numbers of AVs in human BE compared to normal squamous or EAC, and suggest that autophagy functions to improve cell survival after acid reflux injury. Autophagy may thus play a critical role in BE pathogenesis and progression. © 2015 Wiley Periodicals, Inc.
(© 2015 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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