Modern concept of biological identification of selenoproteins

Abstract

Humans possess 25 selenoproteins, approximately half of which are enzymes (selenoenzymes) required for preventing, regulating, or reversing oxidative damage, while others participate in providing calcium metabolism, thyroid hormone maintenance, protein synthesis, cytoskeletal structure etc. This review examines the latest evidences of the biological effects of selenoproteins according to the method of complex analysis of the material. Selenoprotein P promotes insulin resistance in type 2 diabetes, mediates myocardial ischemic-reperfusion injuries and provides protection against disease by reducing chronic oxidative stress. Selenoprotein T is expressed at the endoplasmic reticulum membrane in all cells during development, but is confined to endocrine tissues in adulthood, controls homeostasis of glucose and prevents neurodegeneration by reducing oxidative stress factors. Expression of selenoprotein K is required for efficient Ca2+ flux into melanoma cancer cells, tumour growth and metastasic potential depend on SelK but it suppresses human choriocarcinoma cells. SelK also serves to maintain the normal physiological functions of skeletal muscle. Selenoprotein N deficiency, caused by mutations in the human gene, promotes myopathy characterized by muscle weakness, spinal rigidity, respiratory insufficiency. Sel N participates in normal physiology of skeletal and smooth muscle tissues. Selenoprotein M is located in the endoplasmic reticulum, characterized by high expression in the brain, antioxidative, neuroprotective activity and regulates intracellular Ca2+ levels. Also, the overexpression of SelM was detected in human hepatocellular carcinoma. Selenoprotein S is mentioned as a regulator of ER stress and inflammatory processes. Selenoprotein F controls cell proliferation by the impact on G1period of the cell cycle. Moreover, it is implicated in the pathogenesis of some types of cancer. The Sel F deficiency reduces the migration and invasive ability of the cells. Knockdown of selenoprotein W in rodents leads to increased release of Ca2+, causes oxidative ultramicroscopic injuries of the endoplasmic reticulum and mitochondria ultrastructure, which in turn increases the levels of inflammatory factors. Selenoprotein H is involved in redox regulation, in tumourogenesis. Knockdown of selenoprotein H decreases cellular differentiation and increases proliferation and migration of cells. Selenoproteins U, V, I, O, R are recently identified and their functions are not clearly known. The data analyzed in the review help determine promising directions in the study of the selenoproteins.