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Biochemistry (Moscow)

, Volume 84, Issue 6, pp 637–643 | Cite as

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

  • E. G. NovoselovaEmail author
  • O. V. Glushkova
  • S. B. Parfenuyk
  • M. O. Khrenov
  • S. M. Lunin
  • T. V. Novoselova
  • M. G. Sharapov
  • I. A. Shaev
  • V. I. Novoselov
Article
  • 11 Downloads

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.

Keywords

peroxiredoxin 6 hyperglycemia cytokines RIN-m5F β-cells insulin production signaling cascade NF-ϰB 

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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Notes

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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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • E. G. Novoselova
    • 1
    Email author
  • O. V. Glushkova
    • 1
  • S. B. Parfenuyk
    • 1
  • M. O. Khrenov
    • 1
  • S. M. Lunin
    • 1
  • T. V. Novoselova
    • 1
  • M. G. Sharapov
    • 1
  • I. A. Shaev
    • 1
  • V. I. Novoselov
    • 1
  1. 1.Institute of Cell BiophysicsRussian Academy of SciencesPushchino, Moscow RegionRussia

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