NDLI: Extracellular ATP protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y1 receptor-cAMP signal pathway

Content Provider	Springer Nature Link
Author	Seo, Jong Bae Jung, Seung Ryoung Hille, Bertil Koh, Duk Su
Copyright Year	2016
Abstract	Extracellular adenosine-5′-triphosphate (ATP) regulates cell death and survival of neighboring cells. The detailed effects are diverse depending on cell types and extracellular ATP concentration. We addressed the effect of ATP on ethanol-induced cytotoxicity in epithelial cells, the cell type that experiences the highest concentrations of alcohol. Using pancreatic duct epithelial cells (PDEC), we found that a micromolar range of ATP reverses all intracellular toxicity mechanisms triggered by exceptionally high doses of ethanol and, thus, improves cell viability dramatically. Out of the many purinergic receptors expressed in PDEC, the P2Y1 receptor was identified to mediate the protective effect, based on pharmacological and siRNA assays. Activation of P2Y1 receptors increased intracellular cyclic adenosine monophosphate (cAMP). The protective effect of ATP was mimicked by forskolin and 8-Br-cAMP but inhibited by a protein kinase A (PKA) inhibitor, H-89. Finally, ATP reverted leakiness of PDEC monolayers induced by ethanol and helped to maintain epithelial integrity. We suggest that purinergic receptors reduce extreme alcohol-induced cell damage via the cAMP signal pathway in PDEC and some other types of cells.
Starting Page	229
Ending Page	247
Page Count	19
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	32
Issue Number	3
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-05-20
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Apoptosis Alcohol ATP cAMP Pancreatic duct epithelial cells Purinergic receptor Cell Biology Pharmacology/Toxicology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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