Lipid-peroxidation and peroxiredoxin-overoxidation in the erythrocytes of non-insulin-dependent type 2 diabetic men during acute exercise

Brinkmann, Christian; Blossfeld, Jenny; Pesch, Martin; Krone, Bastian; Wiesiollek, Kathrin; Capin, Dario; Montiel, Georgina; Hellmich, Martin; Bloch, Wilhelm; Brixius, Klara

doi:10.1007/s00421-011-2203-x

Cited by 15 publications

(10 citation statements)

References 44 publications

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“…In line with these ideas, PRDX6 levels were significantly higher in diabetic patients with endothelial dysfunction compared with control subjects, which may possibly represent a physiological adaptation against oxidative stress in patients with atherosclerosis (44). Moreover, another study (45) conducted in diabetic patients demonstrated that physical training was able to increase PRDXs levels measured in erythrocytes, counteracting the oxidative damage that is typical of diabetes. These results are important in outlining the role of the PRDX family in the management of glucose homeostasis and in the prevention of diabetes and cardiovascular disease in diabetic patients, likely reducing the inflammatory state and oxidative stress.…”

Section: Discussionmentioning

confidence: 57%

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Pacifici

Arriga

Sorice³

et al. 2014

Diabetes

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Enhanced oxidative stress contributes to the pathogenesis of diabetes and its complications. Peroxiredoxin 6 (PRDX6) is a key regulator of cellular redox balance, with the peculiar ability to neutralize peroxides, peroxynitrite, and phospholipid hydroperoxides. In the current study, we aimed to define the role of PRDX6 in the pathophysiology of type 2 diabetes (T2D) using PRDX6 knockout (2/2) mice. Glucose and insulin responses were evaluated respectively by intraperitoneal glucose and insulin tolerance tests. Peripheral insulin sensitivity was analyzed by euglycemic-hyperinsulinemic clamp, and molecular tools were used to investigate insulin signaling. Moreover, inflammatory and lipid parameters were evaluated. We demonstrated that PRDX6 2/2 mice developed a phenotype similar to early-stage T2D caused by both reduced glucose-dependent insulin secretion and increased insulin resistance. Impaired insulin signaling was present in PRDX6 2/2 mice, leading to reduction of muscle glucose uptake. Morphological and ultrastructural changes were observed in islets of Langerhans and livers of mutant animals, as well as altered plasma lipid profiles and inflammatory parameters. In conclusion, we demonstrated that PRDX6 is a key mediator of overt hyperglycemia in T2D glucose metabolism, opening new perspectives for targeted therapeutic strategies in diabetes care.A large body of evidence supports a pivotal role for oxidative stress in the etiopathogenesis of insulin resistance (IR) and diabetes (1). Oxidative stress is characterized by an imbalance between reactive oxygen species (ROS) production and antioxidant defense systems. Among all body tissues, pancreatic b-cells are very sensitive to oxidative stress because of their low expression of antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (2). Moreover, hyperglycemia by itself induces IR, increasing oxidative stress injuries, which lead to overt type 2 diabetes (T2D) (3). Interestingly, a relatively new family of antioxidant proteins, the peroxiredoxins (PRDXs), is more highly expressed in pancreatic b-cells (4). Among the six members of this non-seleno peroxidase family, PRDX6 is present in the cytoplasm and is unique because it has peroxidase and also phospholipase A 2 activity (5). Several findings demonstrate the importance of PRDX6 in maintaining redox homeostasis, as follows: lack of PRDX6, in fact, increases the susceptibility to oxidative stress in different tissues (6,7). Nevertheless, data on the relationship between PRDX6 and the pathogenesis of IR and T2D are not available (8). Therefore, we hypothesized that, in terms of physiological status, PRDX6 may play a role in the etiology of IR and diabetes conditions through tissue redox levels. In the current study, we tested our hypothesis in a model of PRDX6 knockout mice (PRDX6 2/2). RESEARCH DESIGN AND METHODS Animal ModelsC57BL/6J wild-type (WT) mice weighing 18-20 g were obtained from The Jackson Laboratory (Bar Harbor, ME), while PRDX6 2/2 mice of mixed background (C57BL6/129SvJ)...

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Section: Discussionmentioning

confidence: 57%

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Pacifici

Arriga

Sorice³

et al. 2014

Diabetes

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“…The precise interaction between these two interventions remains to be established, as exercise training seems to provide no additional benefit when used in combination with caloric restriction [100]. Although individuals with T2D show elevated oxidative stress after maximal-intensity exercise compared to healthy individuals, 12 weeks of preconditioning with regular aerobic training markedly diminished oxidative stress in response to an acute bout of exercise in individuals with T2D [101]. …”

Section: Effects Of Acute and Chronic Exercise On Oxidative Stress Inmentioning

confidence: 99%

The Janus Head of Oxidative Stress in Metabolic Diseases and During Physical Exercise

Pesta

Roden

2017

Curr Diab Rep

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Purpose of ReviewOxidative stress describes an imbalance between production and degradation of reactive oxygen species (ROS), which can damage macromolecules. However, ROS may also serve as signaling molecules activating cellular pathways involved in cell proliferation and adaptation. This review describes alterations in metabolic diseases including obesity, insulin resistance, and/or diabetes mellitus as well as responses to acute and chronic physical exercise.Recent FindingsChronic upregulation of oxidative stress associates with the development of insulin resistance and type 2 diabetes (T2D). While single bouts of exercise can transiently induce oxidative stress, chronic exercise promotes favorable oxidative adaptations with improvements in muscle mitochondrial biogenesis and glucose uptake.SummaryAlthough impaired antioxidant defense fails to scavenge ROS in metabolic diseases, chronic exercising can restore this abnormality. The different metabolic effects are likely due to variability of reactive species and discrepancies in temporal (acute vs. chronic) and local (subcellular distribution) patterns of production.

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“…Increased levels of oxidised PRDX (I–IV) dimers [86] and over-oxidised monomers [70] , [87] , [88] have been reported in immune cells and erythrocytes following exercise. Under cellular oxidative stress, the PRDX decamer can expose an oxidised cysteine that resolves with a neighbouring PRDX thiol to form a stable oxidised dimer.…”

Section: Is Prdx a Peroxide Sensing Protein During And Following Exermentioning

confidence: 99%

“…This ‘over-oxidation’ occurs at a rate too quickly for thiol ‘resolution’ and leads to the formation of over-oxidised monomers. Over-oxidised PRDX monomers have been reported during and following exercise in human peripheral blood mononuclear cells (PBMCs) [93] , [87] and erythrocytes respectively [88] . Formation of over-oxidised PRDX in PBMCs (I–IV isoforms) has been shown to be dependent on the intensity of exercise, with heightened peroxide concentrations during high intensity exercise (80% maximal oxygen consumption [

O 2max ] vs. 60%

O 2max ) likely exceeding the reduction power of TRX, the exclusive reductant of the PRDX (I–IV) disulphide [93] .…”

Section: Is Prdx a Peroxide Sensing Protein During And Following Exermentioning

confidence: 99%

An unexplored role for Peroxiredoxin in exercise-induced redox signalling?

2016

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Peroxiredoxin (PRDX) is a ubiquitous oxidoreductase protein with a conserved ionised thiol that permits catalysis of hydrogen peroxide (H2O2) up to a million times faster than any thiol-containing signalling protein. The increased production of H2O2 within active tissues during exercise is thought to oxidise conserved cysteine thiols, which may in turn facilitate a wide variety of physiological adaptations. The precise mechanisms linking H2O2 with the oxidation of signalling thiol proteins (phosphates, kinases and transcription factors) are unclear due to these proteins' low reactivity with H2O2 relative to abundant thiol peroxidases such as PRDX. Recent work has shown that following exposure to H2O2 in vitro, the sulfenic acid of the PRDX cysteine can form mixed disulphides with transcription factors associated with cell survival. This implicates PRDX as an ‘active’ redox relay in transmitting the oxidising equivalent of H2O2 to downstream proteins. Furthermore, under oxidative stress, PRDX can form stable oxidised dimers that can be secreted into the extracellular space, potentially acting as an extracellular ‘stress’ signal. There is extensive literature assessing non-specific markers of oxidative stress in response to exercise, however the PRDX catalytic cycle may offer a more robust approach for measuring changes in redox balance following exercise. This review discusses studies assessing PRDX-mediated cellular signalling and integrates the recent advances in redox biology with investigations that have examined the role of PRDX during exercise in humans and animals. Future studies should explore the role of PRDX as a key regulator of peroxide mediated-signal transduction during exercise in humans.

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Lipid-peroxidation and peroxiredoxin-overoxidation in the erythrocytes of non-insulin-dependent type 2 diabetic men during acute exercise

Cited by 15 publications

References 44 publications

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

The Janus Head of Oxidative Stress in Metabolic Diseases and During Physical Exercise

An unexplored role for Peroxiredoxin in exercise-induced redox signalling?

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