Protective Effect of Peroxiredoxin 6 Against Toxic Effects of Glucose and Cytokines in Pancreatic RIN-m5F β-Cells

Journal of Diabetes Research

Лунин

et al. 2020

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. We hypothesised that PRDX6, which is well known for its various biological functions, including antioxidant activity, may provide an antidiabetic effect. It was shown that PRDX6 prevented hyperglycemia, lowered the mortality rate, restored the plasma cytokine profile, reversed the splenic cell apoptosis, and reduced the β cell destruction in Langerhans islets in mice with a severe form of alloxan-induced diabetes. In addition, PRDX6 protected rat insulinoma RIN-m5F β cells, cultured with TNF-α and IL-1β, against the cytokine-induced cytotoxicity and reduced the apoptotic cell death and production of ROS. Signal transduction studies showed that PRDX6 prevented the activation of NF-κB and c-Jun N-terminal kinase signaling cascades in RIN-m5F β cells cultured with cytokines. In conclusion, there is a prospect for therapeutic application of PRDX6 to delay or even prevent β cell apoptosis in type 1 diabetes.

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

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

Journal of Diabetes Research

Лунин

et al. 2020

“…The immunomodulatory and anti-inflammatory effect of thymulin was previously shown in mice with septic-type inflammation 11,12 and in mice with experimental autoimmune encephalomyelitis. 13,14 Furthermore, our previous study showed beneficial effects of PRDX6 in RIN-m5F β-cells in vitro 15 and of thymulin in mice with diabetes induced by alloxan administration in vivo. 16,17 In addition, a significant stimulatory effect of PRDX6 on the insulin-producing activity of pancreatic β-cells was demonstrated, and, most importantly, the effect of PRDX6 was detected during culturing the cells under both normal and diabetes-modeling conditions.…”

Section: Introductionmentioning

confidence: 94%

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

Int J Immunopathol Pharmacol

Лунин

et al. 2021

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. We assessed the effects of the drugs on the physiological status of diabetic mice by measuring blood glucose, body weight, and cell counts in several organs, as well as effects of thymulin and PRDX6 on the immune status of diabetic mice measuring concentrations of pro-inflammatory cytokines in blood plasma (TNF-α, interleukin-5 and 17, and interferon-γ), activity of NF-κB and JNK pathways, and Hsp90α expression in immune cells. Both thymulin and PRDX6 reduced the physiological impairments in diabetic mice at various levels. Thymulin and PRDX6 provide beneficial effects in the model of diabetes via very different mechanisms. Taken together, the results of our study indicated that the thymic peptide and the antioxidant enzyme have anti-inflammatory functions. As increasing evidences show diabetes mellitus as a distinct comorbidity leading to acute respiratory distress syndrome and increased mortality in patients with COVID-19 having cytokine storm, thymulin, and PRDX6 might serve as a supporting anti-inflammatory treatment in the therapy of COVID 19 in diabetic patients.

“…Considering that the hyperglycemia associated pathological effects are largely mediated by ROS forma tion, it is plausible that Prdx6 would be able to markedly limit oxidative stress in mice with T1D. Indeed, direct examination of the effect of Prdx6 on ROS levels in the RIN m5F cells in the presence of high glucose level con firmed substantial ROS reduction after addition of Prdx6 to the cultured pancreatic beta cells [80]. Interestingly, it has been found previously that the glucose fluctuations per se correlated to a greater extent with the onset of oxidative stress than with the chronic sustained hyper glycemia [81].…”

Section: Protective Effects Of Peroxiredoxin 6 In Various Models Of Type 1 Diabetesmentioning

confidence: 99%

“…Moreover, in vitro experiments with Prdx6 showed that it protects rat insulinoma (RIN m5F) beta cells exposed to TNF α and IL 1β by decreasing ROS production and cell apoptosis. Investigation of the mechanism of protective activity of the enzyme showed that Prdx6 prevents activation of the signaling pathways NF κB and JNK in the RIN m5F beta cells co cultured with cytokines [80].…”

Section: Protective Effects Of Peroxiredoxin 6 In Various Models Of Type 1 Diabetesmentioning

confidence: 99%

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

Хренов

et al. 2021

Biochemistry Moscow

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 signal ing 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 pancre atic beta cells that produce insulin. Lack of insulin causes hyperglycemia and the need for lifelong injections of insulin in patients with T1D, which, nevertheless, does not exclude damage to many organs and tissues, given particular vulnerabili ty of the blood vessels under conditions of hyperglycemia. The review discusses the role of oxidative stress as a factor that plays a major role in damage of vascular system and pancreatic tissue during the development of T1D. Considering high sen sitivity of pancreatic beta cells to the action of reactive oxygen species (ROS), the possibility of using antioxidants for reduc ing the level of pathological consequences in the course of T1D development is discussed. New information on anti diabetic activity of the exogenous antioxidant enzyme peroxiredoxin 6, which is capable of penetrating cells, activating insulin pro duction in beta cells, reducing ROS levels, as well as decreasing activation of some signaling cascades, production of pro inflammatory cytokines, and expression of Toll like receptors in beta cells and in immune cells during T1D development is discussed.