Effects of perfluorooctanoic acid on endoplasmic reticulum stress and lipid metabolism-related genes in human pancreatic cells

被引:1
作者
Abudayyak, Mahmoud [1 ]
Karaman, Ecem Fatma [2 ]
Guler, Zeynep Rana [1 ,3 ]
Ozden, Sibel [1 ,4 ]
机构
[1] Istanbul Univ, Fac Pharm, Dept Pharmaceut Toxicol, Istanbul, Turkiye
[2] Biruni Univ, Fac Pharm, Dept Pharmaceut Toxicol, Istanbul, Turkiye
[3] Istanbul Univ, Inst Grad Studies Hlth Sci, Istanbul, Turkiye
[4] Istanbul Univ, Fac Pharm, Dept Pharmaceut Toxicol, TR-34116 Istanbul, Turkiye
关键词
Endoplasmic reticulum stress; Epigenetics; Metabolism-related genes; Pancreatitis; Perfluorooctanoic acid; PERFLUOROALKYL SUBSTANCES; GLUCOSE-HOMEOSTASIS; OXIDATIVE STRESS; EXPOSURE; EXPRESSION; PFOA; MOUSE; LIVER; METHYLATION; ASSOCIATION;
D O I
10.1016/j.etap.2023.104083
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Perfluorooctanoic acid (PFOA) is environmentally persistent and has been classified by The International Cancer Research Agency (IARC) as a possible human pancreatic carcinogen. In this study, the epigenetic alteration, the changes in the expression levels of endoplasmic reticulum stress-related and metabolism-related genes, as well as DNA methyltransferase expression were investigated using RT-PCR and ELISA assays. PFOA induced a significant increase in the methylation ratio (5-mC%), impacted DNA methylation maintenance gene expression and decreased lipid metabolism-related genes except for PPAR gamma (>= 13-fold increase). While PFOA induced the expression of ATF4 (>= 5.41-folds), CHOP (>= 5.41-folds) genes, it inhibited the expression of ATF6 (>= 67.2%), GRP78 (>= 64.3%), Elf2 alpha (>= 95.8%), IRE1 (>= 95.5%), and PERK (>= 91.7%) genes. It is thought that epigenetic mechanisms together with disruption in the glucose-lipid metabolism and changes in endoplasmic reticulum stress-related genes may play a key role in PFOA-induced pancreatic toxicity.
引用
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页数:10
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