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

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E. G. Novoselova^1,a*, O. V. Glushkova¹, S. B. Parfenuyk¹, M. O. Khrenov¹, S. M. Lunin¹, T. V. Novoselova¹, M. G. Sharapov¹, I. A. Shaev¹, and V. I. Novoselov¹

¹Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received January 14, 2019; Revised March 18, 2019; Accepted March 18, 2019

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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 pro-inflammatory 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 β-cells from hyperglycemia, reducing the death of these cells by several fold. A measurement of insulin secretion by the RIN-m5F β-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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KEY WORDS: peroxiredoxin 6, hyperglycemia, cytokines, RIN-m5F β-cells, insulin production, signaling cascade NF-κB

DOI: 10.1134/S0006297919060063

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