Dicarbonyl-Modified Low-Density Lipoproteins Are Key Inducers of LOX-1 and NOX1 Gene Expression in the Cultured Human Umbilical Vein Endotheliocytes.

Expression of LOX-1 and NOX1 genes in the human umbilical vein endotheliocytes (HUVECs) cultured in the presence of low-density lipoproteins (LDL) modified with various natural dicarbonyls was investigated for the first time. It was found that among the investigated dicarbonyl-modified LDLs (malondialdehyde (MDA)-modified LDLs, glyoxal-modified LDLs, and methylglyoxal-modified LDLs), the MDA-modified LDLs caused the greatest induction of the LOX-1 and NOX1 genes, as well as of the genes of antioxidant enzymes and genes of proapoptotic factors in HUVECs. Key role of the dicarbonyl-modified LDLs in the molecular mechanisms of vascular wall damage and endothelial dysfunction is discussed.

The Role of Phospholipase Activity of Peroxiredoxin 6 in Its Transmembrane Transport and Protective Properties.

Peroxiredoxin 6 (Prdx6) is a multifunctional eukaryotic antioxidant enzyme. Mammalian Prdx6 possesses peroxidase activity against a wide range of organic and inorganic hydroperoxides, as well as exhibits phospholipase A2 (aiPLA2) activity, which plays an important role in the reduction of oxidized phospholipids and cell membrane remodeling. Exogenous Prdx6 has recently been shown to be able to penetrate inside the cell.

Role of Glutathione Peroxidases and Peroxiredoxins in Free Radical-Induced Pathologies.

In this review, we discuss the pathogenesis of some socially significant diseases associated with the development of oxidative stress, such as atherosclerosis, diabetes, and radiation sickness, as well as the possibilities of the therapeutic application of low-molecular-weight natural and synthetic antioxidants for the correction of free radical-induced pathologies. The main focus of this review is the role of two phylogenetically close families of hydroperoxide-reducing antioxidant enzymes peroxiredoxins and glutathione peroxidases - in counteracting oxidative stress. We also present examples of the application of exogenous recombinant antioxidant enzymes as therapeutic agents in the treatment of pathologies associated with free-radical processes and discuss the prospects of the therapeutic use of exogenous antioxidant enzymes, as well as the ways to improve their therapeutic properties.

Thymulin and peroxiredoxin 6 have protective effects against streptozotocin-induced type 1 diabetes in mice.

Protective effects of peroxiredoxin 6 (PRDX6) in RIN-m5F β-cells and of thymulin in mice with alloxan-induced diabetes were recently reported. The present work was aimed at studying the efficiency of thymulin and PRDX6 in a type 1 diabetes mellitus model induced by streptozotocin in mice. Effects of prolonged treatment with PRDX6 or thymic peptide thymulin on diabetes development were evaluated.

Peroxiredoxin 6 Attenuates Alloxan-Induced Type 1 Diabetes Mellitus in Mice and Cytokine-Induced Cytotoxicity in RIN-m5F Beta Cells.

Type 1 diabetes is associated with the destruction of pancreatic beta cells, which is mediated via an autoimmune mechanism and consequent inflammatory processes. In this article, we describe a beneficial effect of peroxiredoxin 6 (PRDX6) in a type 1 diabetes mouse model. The main idea of this study was based on the well-known data that oxidative stress plays an important role in pathogenesis of diabetes and its associated complications.

Comparative Study of Protective Action of Exogenous 2-Cys Peroxiredoxins (Prx1 and Prx2) Under Renal Ischemia-Reperfusion Injury.

The pathogenesis of ischemia-reperfusion (I/R) injuries is based on oxidative stress caused by a sharp increase in the concentration of free radicals, reactive oxygen species (ROS) and secondary products of free radical oxidation of biological macromolecules during reperfusion. Application of exogenous antioxidants lowers the level of ROS in the affected tissues, suppresses or adjusts the course of oxidative stress, thereby substantially reducing the severity of I/R injury. We believe that the use of antioxidant enzymes may be the most promising line of effort since they possess higher efficiency than low molecular weight antioxidants.

Radioprotective Role of Peroxiredoxin 6.

Peroxiredoxin 6 (Prdx6) is a member of an evolutionary ancient family of peroxidase enzymes with diverse functions in the cell. Prdx6 is an important enzymatic antioxidant. It reduces a wide range of peroxide substrates in the cell, thus playing a leading role in the maintenance of the redox homeostasis in mammalian cells.

Vascular Pathology of Ischemia/Reperfusion Injury of Rat Small Intestine.

Ischemia/reperfusion (I/R) injury of the small intestine caused by occlusion of the superior mesenteric artery affects the intestinal tissue as well as components of the blood circulatory system from the microvasculature to mesenteric vessels. The aim of this work was to study the correlation between the dynamics of destruction development in the intestinal tissue, microvasculature, and mesenteric vessels in I/R of the small intestine. The microvasculature was analyzed by whole-organ continuous monitoring of the intestinal mucosal blood perfusion by laser Doppler flowmetry during the entire I/R.