Selenium (Se) is one of the essential trace elements; its deficiency induces ROS production and cell death in cardiomyocytes, skeletal muscle cells, and vascular smooth muscle cells, but it is still not clear the impact of Se deficiency on human uterine smooth muscle cells (HUSMCs). To investigate the effect of low Se on the mRNA expression of selenoproteins, the mRNA and protein expression of apoptosis and necroptosis of HUSMCs and their mechanism, Se deficient HUSMCs mode was established through culturing with 1% FBS containing 0 ng/mL, 0.7 ng/mL, and 7 ng/mL Se, and 10% FBS was as the control group. Then, the apoptosis and necroptosis rates, intracellular ROS content and the expression levels of selenoproteins, apoptosis, necroptosis, MAPK pathway-related genes were examined under different Se concentrations. The results showed that Se deficiency led to the augment of cell apoptosis and necroptosis in HUSMCs (p < 0.05), downregulated (p < 0.05) 19 selenoproteins (GPX1, GPX2, GPX3, GPX4, GPX6, Dio3, Txnrd2, Txnrd3, SEPHS2, SEL15, SELH, SELI, SELM, SELN, SELO, SELS, SELT, SELV, and SELW), while Dio2, SELK, Txnrd1, and MSRB1 were not affected by Se deficiency (p ≥ 0.05). In addition, Se deficiency led to increased intracellular ROS content, p-P38 and p-JNK gene expression levels (p < 0.05), the mitochondrial apoptosis pathway Bax, Casp9 and Cle-Casp3 protein expression levels (p < 0.05), and decreased Bcl2 protein expression level (p < 0.05), simultaneously, increased necroptosis marker genes RIP1, RIP3, and MLKL protein expression levels (p < 0.05) with a dose-dependent pattern. The above results indicate that Se deficiency induces HUSMCs apoptosis and necroptosis through the ROS/MAPK pathway and is closely related to selenoproteins.

中文翻译：

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硒缺乏通过人子宫平滑肌细胞中的 ROS/MAPK 信号诱导凋亡和坏死性凋亡。

硒（Se）是人体必需的微量元素之一；硒的缺乏会导致心肌细胞、骨骼肌细胞和血管平滑肌细胞产生 ROS 和细胞死亡，但尚不清楚硒缺乏对人子宫平滑肌细胞 (HUSMCs) 的影响。为研究低硒对 HUSMCs 硒蛋白 mRNA 表达、凋亡和坏死性凋亡的 mRNA 和蛋白表达的影响及其机制，采用含 0 ng/mL、0.7 ng/mL 的 1% FBS 培养建立缺硒 HUSMCs 模式。 mL, 7 ng/mL Se, 10% FBS 作为对照组。然后，检测不同硒浓度下细胞凋亡和坏死性凋亡率、细胞内活性氧含量以及硒蛋白、凋亡、坏死性凋亡、MAPK通路相关基因的表达水平。结果表明，硒缺乏导致 HUSMC 细胞凋亡和坏死性凋亡增加（p < 0.05），下调（p < 0.05）19 种硒蛋白（GPX1、GPX2、GPX3、GPX4、GPX6、Dio3、Txnrd2、Txnrd3、SEPHS2、 SEL15、SELH、SELI、SELM、SELN、SELO、SELS、SELT、SELV 和 SELW），而 Dio2、SELK、Txnrd1 和 MSRB1 不受硒缺乏的影响（p ≥ 0.05）。此外，硒缺乏导致细胞内 ROS 含量、p-P38 和 p-JNK 基因表达水平升高（p < 0.05），线粒体凋亡途径 Bax、Casp9 和 Cle-Casp3 蛋白表达水平升高（p < 0.05），并降低Bcl2 蛋白表达水平 (p < 0.05) 同时以剂量依赖性模式增加坏死性凋亡标记基因 RIP1、RIP3 和 MLKL 蛋白表达水平 (p < 0.05)。