Chen Jian, Mita Yuichiro, Noguchi Noriko
The Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Tatara-Miyakodani, Kyotanabe 610-0394, Japan.
J Clin Biochem Nutr. 2024 Sep;75(2):125-132. doi: 10.3164/jcbn.23-104. Epub 2024 May 24.
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.
饮酒被认为是糖尿病发生的危险因素之一。最近，有报道称血液中硒蛋白P水平会因乙醇摄入而升高。然而，乙醇增加硒蛋白P的机制尚未阐明。当用人肝脏来源的HepG2细胞用乙醇处理时，硒蛋白P蛋白及其mRNA的表达呈浓度和时间依赖性增加。已知调节硒蛋白P转录的AMPK和JNK蛋白水平不受乙醇处理的影响。然而，硒蛋白P的转录因子核FoxO3a的量增加了。这与ERK1而非ERK2的去磷酸化有关。发现ERK1通过双特异性磷酸酶5和双特异性磷酸酶6的激活而去磷酸化。然而，ERK磷酸激酶对MEK的磷酸化不受乙醇处理的影响。这些结果表明，乙醇诱导的硒蛋白P水平升高是通过DUSP5/6-ERK1-FoxO3a途径增强硒蛋白P mRNA的转录而发生的。
