{"title":"Ethanol enhances selenoprotein P expression via ERK-FoxO3a axis in HepG2 cells.","authors":"Jian Chen, Yuichiro Mita, Noriko Noguchi","doi":"10.3164/jcbn.23-104","DOIUrl":null,"url":null,"abstract":"<p><p>Drinking alcohol is considered one of the risk factors for development of diabetes mellitus. Recently, it was reported that selenoprotein P levels in blood are increased by ethanol intake. However, the mechanism by which ethanol increases selenoprotein P has not been elucidated. The expression of selenoprotein P protein and its mRNA were increased in a concentration- and time-dependent manner when human liver-derived HepG2 cells were treated with ethanol. Levels of AMPK and JNK proteins, which have been known to regulate selenoprotein P transcription, were unchanged by ethanol treatment. However, the amount of nuclear FoxO3a, a transcription factor of SeP, was increased. This was associated with dephosphorylation of ERK1 but not ERK2. It was found that ERK1 was dephosphorylated by activation of dual-specific phosphatase 5 and dual-specific phosphatase 6. However, the phosphorylation of MEK by ERK phosphokinase was not affected by ethanol treatment. These results suggest that the ethanol-induced increase in SeP levels occurs by enhanced transcription of SeP mRNA via the DUSP5/6-ERK1-FoxO3a pathway.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"75 2","pages":"125-132"},"PeriodicalIF":2.0000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425072/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Biochemistry and Nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3164/jcbn.23-104","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/24 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Drinking alcohol is considered one of the risk factors for development of diabetes mellitus. Recently, it was reported that selenoprotein P levels in blood are increased by ethanol intake. However, the mechanism by which ethanol increases selenoprotein P has not been elucidated. The expression of selenoprotein P protein and its mRNA were increased in a concentration- and time-dependent manner when human liver-derived HepG2 cells were treated with ethanol. Levels of AMPK and JNK proteins, which have been known to regulate selenoprotein P transcription, were unchanged by ethanol treatment. However, the amount of nuclear FoxO3a, a transcription factor of SeP, was increased. This was associated with dephosphorylation of ERK1 but not ERK2. It was found that ERK1 was dephosphorylated by activation of dual-specific phosphatase 5 and dual-specific phosphatase 6. However, the phosphorylation of MEK by ERK phosphokinase was not affected by ethanol treatment. These results suggest that the ethanol-induced increase in SeP levels occurs by enhanced transcription of SeP mRNA via the DUSP5/6-ERK1-FoxO3a pathway.
期刊介绍:
Journal of Clinical Biochemistry and Nutrition (JCBN) is
an international, interdisciplinary publication encompassing
chemical, biochemical, physiological, pathological, toxicological and medical approaches to research on lipid peroxidation, free radicals, oxidative stress and nutrition. The
Journal welcomes original contributions dealing with all
aspects of clinical biochemistry and clinical nutrition
including both in vitro and in vivo studies.