{"title":"乙醇通过 ERK-FoxO3a 轴增强 HepG2 细胞中硒蛋白 P 的表达。","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":"{\"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}","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
摘要
饮酒被认为是导致糖尿病的危险因素之一。最近有报道称,摄入乙醇会增加血液中硒蛋白 P 的含量。然而,乙醇增加硒蛋白 P 的机制尚未阐明。乙醇处理人肝源性 HepG2 细胞时,硒蛋白 P 蛋白及其 mRNA 的表达呈浓度和时间依赖性增加。已知可调控硒蛋白 P 转录的 AMPK 和 JNK 蛋白的水平在乙醇处理后保持不变。然而,核 FoxO3a(一种 SeP 转录因子)的含量却增加了。这与 ERK1 的去磷酸化有关,但与 ERK2 无关。研究发现,ERK1 通过激活双特异性磷酸酶 5 和双特异性磷酸酶 6 而去磷酸化。然而,ERK 磷酸激酶对 MEK 的磷酸化作用不受乙醇处理的影响。这些结果表明,乙醇诱导的 SeP 含量增加是通过 DUSP5/6-ERK1-FoxO3a 途径增强 SeP mRNA 的转录实现的。
Ethanol enhances selenoprotein P expression via ERK-FoxO3a axis in HepG2 cells.
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.