Abstract
Taking into account a special role of pancreatic β-cells in the development of diabetes mellitus, the effects of peroxiredoxin 6 (Prx6) on the viability and functional activity of rat insulinoma RIN-m5F β-cells were studied under diabetes-simulating conditions. For this purpose, the cells were cultured at elevated glucose concentrations or in the presence of proinflammatory cytokines (TNF-α and IL-1) known for their special role in the cytotoxic autoimmune response in diabetes. It was found that the increased glucose concentration of 23-43 mM caused death of 20-60% β-cells. Prx6 added to cells significantly reduced the level of reactive oxygen species and protected the RIN-m5F ß-cells from hyperglycemia, reducing the death of these cells by several fold. A measurement of insulin secretion by the RIN-m5F ß-cells showed a significant stimulatory effect of Prx6 on the insulin-producing activity of pancreatic β-cells. It should be noted that the stimulatory activity of Prx6 was detected during culturing the cells under both normal and unfavorable conditions. The regulation of the NF-ϰB signaling cascade could be one of the mechanisms of Prx6 action on β-cells, in particular, through activation of RelA/p65 phosphorylation at Ser536.
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Abbreviations
- carboxy-H2DCFDA:
-
5-(and 6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate (general oxidative stress indicator)
- GPx:
-
glutathione peroxidase
- IL:
-
interleukin
- NF-ϰB:
-
nuclear factor kappa-B
- Prx6:
-
peroxiredoxin 6
- RIN-m5F cells:
-
rat insulinoma cells
- ROS:
-
reactive oxygen species
- SOD:
-
superoxide dismutase
- TNF-α:
-
tumor necrosis factor alpha
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Acknowledgements
In the work, we used the equipment of the Pushchino Scientific Center Collective Use Center (an Infinite 200 plate reader; Tecan, Austria).
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Russian Text © The Author(s), 2019, published in Biokhimiya, 2019, Vol. 84, No. 6, pp. 819-826.
Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19-011, April 29, 2019.
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Novoselova, E.G., Glushkova, O.V., Parfenuyk, S.B. et al. Protective Effect of Peroxiredoxin 6 Against Toxic Effects of Glucose and Cytokines in Pancreatic RIN-m5F β-Cells. Biochemistry Moscow 84, 637–643 (2019). https://doi.org/10.1134/S0006297919060063
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DOI: https://doi.org/10.1134/S0006297919060063