Selenium compounds in redox regulation of inflammation and apoptosis

Abstract

Monocytes and macrophages play a key role in the development of inflammation: under the action of lipopolysaccharides (LPS), absorbed from the intestine, monocytes and macrophages form reactive oxygen species (ROS) and cytokines, this leads to the development of oxidative stress, inflammation and/or apoptosis in all types of tissues. In the cells LPS induce an “internal” TLR4-mediated MAP-kinase inflammatory signaling pathway and cytokines through the superfamily of tumor necrosis factor receptor (TNFR) and the “death domain” (DD) initiate an “external” caspase apoptosis cascade or necrosis activation that causes necroptosis. Many of the proteins involved in intracellular signaling cascades (MYD88, ASK1, IKKa/b, NF-kB, AP-1) are redox-sensitive and their activity is regulated by antioxidants thioredoxin, glutaredoxin, nitroredoxin, and glutathione. Oxidation of these signaling proteins induced by ROS enhances the development of inflammation and apoptosis, and their reduction with antioxidants, on the contrary, stabilizes the signaling cascades speed, preventing the vicious circle of oxidative stress, inflammation and apoptosis that follows it. Antioxidant (AO) enzymes thioredoxin reductase (TRXR), glutaredoxin reductase (GLRXR), glutathione reductase (GR) are required for reduction of non-enzymatic antioxidants (thioredoxin, glutaredoxin, nitroredoxin, glutathione), and AO enzymes (SOD, catalase, GPX) are required for ROS deactivation. The key AO enzymes (TRXR and GPX) are selenium-dependent; therefore selenium deficiency leads to a decrease in the body's antioxidant defense, the development of oxidative stress, inflammation, and/or apoptosis in various cell types. Nrf2-Keap1 signaling pathway activated by selenium deficiency and/or oxidative stress is necessary to restore redox homeostasis in the cell. In addition, expression of some genes is changed with selenium deficiency. Consequently, growth and proliferation of cells, their movement, development, death, and survival, as well as the interaction between cells, the redox regulation of intracellular signaling cascades of inflammation and apoptosis, depend on the selenium status of the body. Prophylactic administration of selenium-containing preparations (natural and synthetic (organic and inorganic)) is able to normalize the activity of AO enzymes and the general status of the body. Organic selenium compounds have a high bioavailability and, depending on their concentration, can act both as selenium donors to prevent selenium deficiency and as antitumor drugs due to their toxicity and participation in the regulation of signaling pathways of apoptosis. Known selenorganic compounds diphenyldiselenide and ethaselen share similarity with the Russian organo selenium compound, diacetophenonylselenide (DAPS-25), which serves as a source of bioavailable selenium, exhibits a wide range of biological activity, including antioxidant activity, that governs cell redox balance, inflammation and apoptosis regulation.

GPX8 promotes migration and invasion by regulating epithelial characteristics in non‐small cell lung cancer

“…The GPX family have also been reported to be able to stabilize the signaling cascades speed and prevent the vicious circle of oxidative stress and apoptosis. 17 Suzuki et al also found that the expression of GPX2 in rat hepatoma cells was not only related to cell proliferation, but also related to tumor invasion and metastasis . 18 Our previous results coincided with those mentioned in these studies.…”

IRGM/Irgm1 Aggravates Progression of Atherosclerosis by Inducing Macrophage Apoptosis through the MAPK Signaling Pathway

“…Various hypotheses have been proposed to explain the apoptosis of macrophages in advanced atherosclerosis, such as deprivation of growth factors or the presence of toxic cytokines (51,52), yet there is no evidence for these hypotheses in vivo. Several studies have pointed out that an increased accumulation of ROS, the product of endoplasmic reticulum stress, activates MAPK, which in turn causes the release of the mitochondrial pro-apoptotic proteins caspase3/7/9, subsequently leading to cell apoptosis (53,54).…”

Cyclic Peptide D7 Promotes Osteogenesis and Inhibits Osteoclastogenesis by Regulating Redox Balance of Bone Remodeling

“…It can be seen that ROS induce osteoblast apoptosis, which is bene cial to the generation of osteoclasts [38]. In addition, intracellular ROS must be degraded by antioxidants, such as Cu/Zn SOD, Mn SOD, CAT, GPX, and GR [39]. D7 balances the production of intracellular ROS by increasing the level of antioxidant enzymes, which balances the levels of ROS and antioxidants in the cell to protect it from ROS damage.…”