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Docosahexaenoic acid inhibits ethanol/palmitoleic acid-induced necroptosis in AR42J cells

Authors
 L Ku  ;  J Lee  ;  J W Lim  ;  L Jin  ;  J T Seo  ;  H Kim 
Citation
 JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, Vol.71(3) : 437-450, 2020-06 
Journal Title
 JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 
ISSN
 0867-5910 
Issue Date
2020-06
Abstract
Fatty acid ethyl esters (FAEEs), non-oxidative metabolites of ethanol, are the main causative agents of severe acute pancreatitis resulting from alcohol abuse. Pancreatic acinar cells exposed to ethanol in combination with the fatty acid palmitoleic acid (EtOH/POA) display increased levels of palmitoleic acid ethyl ester and cell death. Oxidative stress and acinar cell necroptosis are implicated in the pathology of severe acute pancreatitis. Docosahexaenoic acid (DHA) serves as a powerful anti-oxidant that reduces pancreatic inflammation and improves the outcomes of patients with acute pancreatitis. We investigated whether treatment of EtOH/POA, as an in vitro model of alcoholic pancreatitis, increases reactive oxygen species (ROS), necroptosis-regulating proteins, and cell death by increasing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and intracellular calcium. Also, we investigated whether DHA inhibits EtOH/POA-induced alterations in pancreatic acinar AR42J cells. As a result, EtOH/POA increased intracellular and mitochondrial ROS levels, NADPH oxidase activity, necroptosis-regulating proteins, and cell death, which was inhibited by NADPH oxidase inhibitor apocynin, the Ca2+ chelator BAPTA, and DHA. However, DHA did not reduce EtOH/POA-induced increases in Ca2+ oscillation or levels in AR42J cells. Furthermore, EtOH/POA induced mitochondrial dysfunction by reducing mitochondrial membrane polarization and hence, adenosine triphosphate (ATP) production. DHA treatment attenuated EtOH/POA-induced mitochondrial dysfunction. In conclusion, DHA inhibits EtOH/POA-induced necroptosis by suppressing NADPH oxidase activity, reducing ROS levels, preventing mitochondrial dysfunction, and inhibiting activation of necroptosis-regulating proteins in AR42J cells.
Files in This Item:
T202004511.pdf Download
DOI
10.26402/jpp.2020.3.15
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180259
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