Selenium Deficiency Induces Apoptosis and Necroptosis Through ROS/MAPK Signal in Human Uterine Smooth Muscle Cells

Biol Trace Elem Res. 2022 Jul;200(7):3147-3158. doi: 10.1007/s12011-021-02910-z. Epub 2021 Sep 4.

Abstract

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.

Keywords: Apoptosis; Human uterine smooth muscle; Necroptosis; Selenium deficiency; Selenoproteins.

MeSH terms

  • Animals
  • Apoptosis
  • Chickens / metabolism
  • Humans
  • MAP Kinase Signaling System
  • Myocytes, Smooth Muscle / metabolism
  • Necroptosis
  • RNA, Messenger / genetics
  • Reactive Oxygen Species
  • Selenium*
  • Selenoproteins / genetics
  • Selenoproteins / metabolism

Substances

  • RNA, Messenger
  • Reactive Oxygen Species
  • Selenoproteins
  • Selenium