Protective functions of peroxiredoxin-1 against cytokine-induced MIN6 pancreatic β-cell line death

Abstract

Pancreatic β-cells play a crucial role in glucose homeostasis, and the failure of these cells to function results in the development of type 1 diabetes (T1D). The MIN6 cell line, which closely resembles pancreatic β-cells, was used to unravel the relationship between pancreatic β-cell function and the antioxidant enzyme PRX-1. PRX-1 was knocked down in MIN6 cells using a shPRX-1 lentiviral construct, and a mixture of inflammatory cytokines was administered to challenge the MIN6 cells. Nitric oxide (NO) production and inducible NO synthase (iNOS) expression were elevated in shPRX-1 compared with the control. Also, shPRX-1 transduced cells showed higher levels of NF-κB nuclear translocation, suggesting that PRX-1 has a regulatory role in NF-κB nuclear translocation and iNOS expression. In correlation with NO levels, decreased anti-apoptotic gene Bcl-xl level and elevated pro-apoptotic gene Bim levels were observed in shPRX-1 cells compared with scramble, and cell viability decreased accordingly. A rescue experiment was performed subsequently using an iNOS inhibitor to confirm NO as the cause of cell death. Overall, the results of this study suggest possible protective roles of the antioxidant enzyme PRX-1 in the insulinoma cell line MIN6 and possibly in pancreatic β-cells under T1D conditions.

Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response

“…An important role in the elimination of peroxides generated during the oxidative protein folding in the ER play peroxiredoxins [44]. In beta-cells, they protect from oxidative stress [45,46] and improve insulin secretion [47]. In our study, peroxiredoxin-1 (PRDX1), peroxiredoxin-2 (PRDX2) and peroxiredoxin-4 (PRDX4) were significantly decreased in the presence of palmitate.…”

Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

“…When over‐oxidized, peroxiredoxin‐1 has an additional function as a chaperone as well . The protective effects of peroxiredoxin‐1, peroxiredoxin‐2, and peroxiredoxin‐3 against cytokine‐ and oxidative stress‐induced apoptosis in β‐cells have already been demonstrated . In addition, increased peroxiredoxin‐1 expression has also been found in the islets of Zucker Diabetic Fatty rats compared to Zucker Lean and Zucker Fatty rats, in INS‐1E β‐cells treated with oleate and in INS‐1E β‐cells treated with palmitate under hyperglycemic conditions .…”

Peroxiredoxin I deficiency increases pancreatic β‑cell apoptosis after streptozotocin stimulation via the AKT/GSK3β signaling pathway

“…Establishment of Prx I-knockdown stable cell line. For the construction of lentivirus packaging Prx i short hairpin (sh)rna, control scrambled shrna (5'-TTc Tcc Gaa cGT GTc acG TTT c-3') and shrnas specifically targeting Prx i (5'-caGTGaTaGaGccGaT-3') were synthesized and inserted into the pGlV3/H1/GFP+Puro lentiviral vector (Shanghai GenePharma co., ltd.) (26). Prior to viral infection, Min6 cells were seeded in 6-wells plate at the density of 3x10 5 cells/well and cultured to 70-80% confluence.…”

“…Patients with type II diabetes present higher plasma levels of Prx I, compared with healthy individuals, which was reported as an indicator of glycemic control in type II diabetes ( 25 ). Pancreatic β-cell apoptosis and function decline have been implicated not only in type I and type II diabetes, but also in pancreatic transplantation ( 26 ).…”