The role of TLR4/NF-κB signaling in the radioprotective effects of exogenous Prdx6

Шарапов, М. Г.; Глушкова, О. В.; Parfenyuk, Svetlana B.; Gudkov, Sergey V.; Лунин, С. М.; Новоселова, Е. Г.

doi:10.1016/j.abb.2021.108830

Cited by 24 publications

(26 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of some antioxidant response system genes, for which the most significant change in expression after irradiation of 3T3 cells was previously shown, was assessed [ 8 ]. Interestingly, X-ray irradiation with a dose of 6 Gy resulted in a prolonged activation of the expression of isoforms PRDX2, PRDX3, and PRDX4, while the expression level of PRDX1, PRDX5, and PRDX6 did not differ significantly from the control values ( Figure 3 A).…”

Section: Resultsmentioning

confidence: 99%

“…It was shown that peroxiredoxins (Prdxs), an evolutionarily ancient family of peroxidases capable of reducing a wide range of inorganic and organic peroxide substrates, may play an important role in radioprotection [ 6 , 7 ]. It should be noted that we have recently demonstrated penetration of exogenous Prdx6 into the cells using FITC-labeled Prdx6 [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, we recently demonstrated that preliminarily applied Prdx6 protected 3T3 mouse fibroblasts against LD50 X-ray irradiation in vitro. Thus, pretreatment with Prdx6 increased cell survival, stimulated proliferation, normalized the level of ROS in the culture, and suppressed apoptosis and necrosis in 3T3 fibroblasts [ 8 ]. We believe that it is equally important to test whether Prdx6 is capable of exerting a radioprotective effect when applied several hours after irradiation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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. Our results suggested that Prdx6 treatment normalized p53 and NF-κB/p65 expression, p21 levels, DNA repair-associated genes (XRCC4, XRCC5, H2AX, Apex1), TLR expression, cytokine production (TNF-α and IL-6), and apoptosis, as evidenced by decreased caspase 3 level in irradiated 3T3 cells. In addition, Prdx6 treatment reduced senescence, as evidenced by the decreased percentage of SA-β-Gal positive cells in cultured 3T3 fibroblasts. Importantly, the activity of the NRF2 gene, an important regulator of the antioxidant cellular machinery, was completely suppressed by irradiation but was restored by post-irradiation Prdx6 treatment. These data support the radioprotective therapeutic efficacy of Prdx6.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…To elucidate this issue, a recombinant Prdx6 tagged with fluorescein 5 isothiocyanate (FITC) was produced. Cultivation of embryonic fibroblasts 3T3 with the Prdx6-FITC revealed that under normal conditions it binds to cell surface and may penetrate into cells with the amount of protein entering the cells increasing with time of cultivation as well as concentration of added Prdx6-FITC [91]. Hence, the recombinant Prdx6 could enter cells and directly impact antioxidant status of the cell.…”

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

Новоселова

Глушкова

Хренов

et al. 2021

Biochemistry Moscow

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…While the antioxidant function of PRDX6 can be mostly considered as anti-inflammatory, its iPLA2 activity and the ability to release arachidonic acid (AA) has been linked to inflammation in experiments utilizing the iPLA2 activity inhibitor, MJ33 [ 28 , 35 , 36 ]. In addition to the iPLA2 activity, peroxiredoxins, including PRDX6, can be released to extracellular space where they might function as damage-associated molecular patterns (DAMPs [ 37 ]) activating the pro-inflammatory pathways via the TLR4 receptor [ 38 ]. There is a vast research mapping the physiological functions of PRDX6 in multiple organs or cell types such as lungs, brain, eye, or spermatozoa and also pathophysiological functions implying the role of PRDX6 in tumor viability [ [29] , [30] , [31] ], progression, and metastasis [ [39] , [40] , [41] , [42] , [43] ].…”

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape

et al. 2022

View full text Add to dashboard Cite

Cellular senescence is a complex stress response defined as an essentially irreversible cell cycle arrest mediated by the inhibition of cell cycle-specific cyclin dependent kinases. The imbalance in redox homeostasis and oxidative stress have been repeatedly observed as one of the hallmarks of the senescent phenotype. However, a large-scale study investigating protein oxidation and redox signaling in senescent cells in vitro has been lacking. Here we applied a proteome-wide analysis using SILAC-iodoTMT workflow to quantitatively estimate the level of protein sulfhydryl oxidation and proteome level changes in ionizing radiation-induced senescence (IRIS) in hTERT-RPE-1 cells. We observed that senescent cells mobilized the antioxidant system to buffer the increased oxidation stress. Among the antioxidant proteins with increased relative abundance in IRIS, a unique 1-Cys peroxiredoxin family member, peroxiredoxin 6 (PRDX6), was identified as an important contributor to protection against oxidative stress. PRDX6 silencing increased ROS production in senescent cells, decreased their resistance to oxidative stress-induced cell death, and impaired their viability. Subsequent SILAC-iodoTMT and secretome analysis after PRDX6 silencing showed the downregulation of PRDX6 in IRIS affected protein secretory pathways, decreased expression of extracellular matrix proteins, and led to unexpected attenuation of senescence-associated secretory phenotype (SASP). The latter was exemplified by decreased secretion of pro-inflammatory cytokine IL-6 which was also confirmed after treatment with an inhibitor of PRDX6 iPLA2 activity, MJ33. In conclusion, by combining different methodological approaches we discovered a novel role of PRDX6 in senescent cell viability and SASP development. Our results suggest PRDX6 could have a potential as a drug target for senolytic or senomodulatory therapy.

show abstract

The role of TLR4/NF-κB signaling in the radioprotective effects of exogenous Prdx6

Cited by 24 publications

References 73 publications

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

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

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

Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape

Contact Info

Product

Resources

About