Peroxyredoxin 6 Protects RIN-M5F Pancreatic Beta Cells Against Streptozotocin-Induced Senescence.

Background/aims: There are evidences that a decrease in the functional activity of pancreatic β-cells under type 2 diabetes conditions may be associated with their senescence, therefore, senotherapy may be a prospective strategy for the diabetes treatment.

Methods: The senotherapeutic potential of peroxiredoxin 6 (PRDX6) was studied in RIN-m5F pancreatic β-cells with streptozotocin-induced senescence by measuring markers, associated with senescence.

Results: Exposure to streptozotocin (STZ) resulted in the senescence of the β-cells.

Pancreas Β-Cells in Type 1 and Type 2 Diabetes: Cell Death, Oxidative Stress and Immune Regulation. Recently Appearing Changes in Diabetes Consequences.

Diabetes mellitus type 1 (T1D) and type 2 (T2D) develop due to dysfunction of the Langerhans islet β-cells in the pancreas, and this dysfunction is mediated by oxidative, endoplasmic reticulum (ER), and mitochondrial stresses. Although the two types of diabetes are significantly different, β-cell failure and death play a key role in the pathogenesis of both diseases, resulting in hyperglycemia due to a reduced ability to produce insulin. In T1D, β-cell apoptosis is the main event leading to hyperglycemia, while in T2D, insulin resistance results in an inability to meet insulin requirements.

Protective Effects of Peroxiredoxin 6 in Pro-Inflammatory Response Model Using Raw 264.7 Macrophages.

The aim of the work was to study effects of peroxiredoxin 6 (PRDX6), a recombinant antioxidant protein, on the level of pro-inflammatory responses of RAW 264.7 macrophages to endotoxin exposure. Addition of LPS to the RAW 264.

Cell Senescence and Central Regulators of Immune Response.

Pathways regulating cell senescence and cell cycle underlie many processes associated with ageing and age-related pathologies, and they also mediate cellular responses to exposure to stressors. Meanwhile, there are central mechanisms of the regulation of stress responses that induce/enhance or weaken the response of the whole organism, such as hormones of the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic and parasympathetic systems, thymic hormones, and the pineal hormone melatonin. Although there are many analyses considering relationships between the HPA axis and organism ageing, we found no systematic analyses of relationships between the neuroendocrine regulators of stress and inflammation and intracellular mechanisms controlling cell cycle, senescence, and apoptosis.

Peroxiredoxin 6 Applied after Exposure Attenuates Damaging Effects of X-ray Radiation in 3T3 Mouse Fibroblasts.

Although many different classes of antioxidants have been evaluated as radioprotectors, none of them are in widespread clinical use because of their low efficiency. The goal of our study was to evaluate the potential of the antioxidant protein peroxiredoxin 6 (Prdx6) to increase the radioresistance of 3T3 fibroblasts when Prdx6 was applied after exposure to 6 Gy X-ray. In the present study, we analyzed the mRNA expression profiles of genes associated with proliferation, apoptosis, cellular stress, senescence, and the production of corresponding proteins from biological samples after exposure of 3T3 cells to X-ray radiation and application of Prdx6.

Role of Innate Immunity and Oxidative Stress in the Development of Type 1 Diabetes Mellitus. Peroxiredoxin 6 as a New Anti-Diabetic Agent.

The review discusses information on the development of type 1 diabetes mellitus (T1D) as a systemic autoimmune and inflammatory disease. Focus of the review is on the role of innate immune system, including activation of some signaling cascades, cytokine response, and activity of the Toll-like receptors in the development of T1D. Dysfunction of innate immunity is the cause of the attack of pancreatic beta cells by the host T-lymphocytes, which leads to the death of pancreatic beta cells that produce insulin.

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.

Protective Effect of PBCA Nanoparticles Loaded with Thymulin Against the Relapsing-Remitting Form of Experimental Autoimmune Encephalomyelitis in Mice.

Relapsing-remitting experimental autoimmune encephalomyelitis (rEAE) in mice is a model that closely resembles relapsing-remitting multiple sclerosis in humans. This study aims to investigate a new approach to modulation of the inflammatory response in rEAE mice using a thymic peptide thymulin bound to polybutylcyanoacrylate (PBCA) nanoparticles. PBCA nanoparticles were used to prolong the presence of thymulin in the blood.

Effects of low-level combined static and weak low-frequency alternating magnetic fields on cytokine production and tumor development in mice.

We investigated the effects of weak combined magnetic fields (MFs) produced by superimposing a constant MF (in the range 30 - 150 µT) and an alternating MF (100 or 200 nT) on cytokine production in healthy Balb/C male mice exposed 2 h daily for 14 days. The alternating magnetic field was a sum of several frequencies (ranging from 2.5 - 17.

The role of mitochondrial KATP channel in anti-inflammatory effects of uridine in endotoxemic mice.

In this study, we examined the effects of uridine on plasma cytokine levels, heat shock protein (HSP) 72 expression, and nuclear factor (NF)-κB signaling in spleen lymphocytes after exposure of male BALB/c mice to Escherichia coli lipopolysaccharide (LPS). Mice were treated with uridine (30 mg/kg body weight, intraperitoneal injection [i.p.

Extremely low-level microwaves attenuate immune imbalance induced by inhalation exposure to low-level toluene in mice.

Purpose: To clarify whether extremely low-level microwaves (MW) alone or in combination with p38 inhibitor affect immune cell responses to inhalation exposure of mice to low-level toluene.

Materials And Methods: The cytokine profile, heat shock proteins expression, and the activity of several signal cascades, namely, NF-κB, SAPK/JNK, IRF-3, p38 MAPK, and TLR4 were measured in spleen lymphocytes of mice treated to air-delivered toluene (0.6 mg/m) or extremely low-level microwaves (8.

Signaling, stress response and apoptosis in pre-diabetes and diabetes: restoring immune balance in mice with alloxan-induced type 1 diabetes mellitus.

The aim of this study was to compare immune imbalances in "pre-diabetic" and diabetic mice and to evaluate the efficacy of several agents in improving the immunity of mice with type 1 diabetes. Pre-diabetic and diabetic models generated by a single or double alloxan injection were monitored for plasma glucose and pancreas immunohistochemistry. To study the immunity in pre-diabetic and diabetic Balb/C male mice; the levels of cytokines; synthesis of inducible heat shock proteins HSP72 and HSP90α; activity of the NF-κB, IFR3, SAPK/JNK, and TLR4 pathways; and apoptosis levels in thymuses were measured.

The role of the NF-κB, SAPK/JNK, and TLR4 signalling pathways in the responses of RAW 264.7 cells to extremely low-intensity microwaves.

Purpose: To investigate the role of the toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), and stress activated protein kinases/Jun N-terminal kinase (SAPK/JNK) signalling pathways in the responses of RAW 264.7 macrophages to low-intensity microwaves (MW).

Materials And Methods: Three inhibitors of TLR4, SAPK/JNK, and NF-κB signalling, namely CLI-095, SP600125, and IKK Inhibitor XII, respectively, were added to cultured RAW 264.

Inhibitors of TLR-4, NF-κB, and SAPK/JNK signaling reduce the toxic effect of lipopolysaccharide on RAW 264.7 cells.

The present study was designed to examine and compare the effects of three suppressors on the cytokine response in tandem with examining: the synthesis of inducible forms of heat shock proteins; HSP72 and HSP90α; activities of NF-κB and SAPK/JNK signaling pathways; and TLR4 expression. Pre-treatment with inhibitors offers promise as protective means to lower the activity of these cascades, thereby circumventing the formation of excessive amounts of pro-inflammatory molecules. Three inhibitors of TLR4, SAPK/JNK, and NF-κB signaling, namely CLI-095, SP600125, and IKK Inhibitor XII, respectively, were added to cultured RAW 264.

Thymus peptides regulate activity of RAW 264.7 macrophage cells: inhibitory analysis and a role of signal cascades.

Objectives: The aim of this study was to reveal T-lymphocyte-independent mechanisms of thymic peptide-mediated immunomodulation.

Methods: The effects of two thymic peptides- thymulin and thymopentin were studied in cultured RAW 264.7 macrophages (lipopolysaccharide-stimulated or unstimulated) by measuring cytokine production and signal protein levels.

Naturally occurring antioxidant nutrients reduce inflammatory response in mice.

The effects of mixed dietary coenzyme Q(9), alpha-tocopherol, and beta-carotene on immune cell activity and blood cytokine profile were studied in peritoneal macrophages, spleen lymphocytes, and blood plasma from mice with acute inflammation induced by lipopolysaccharide (LPS). The activity of each fat-soluble antioxidant was also investigated separately in several model systems, both in vivo and in vitro. NMRI male mice were fed a diet supplemented with fat-soluble antioxidants for 15 days prior to LPS injection.