Decreased paraoxonase 2 enzymatic activity in monocyte/macrophages cells. A comparative in vivo and in vitro study for diabetes

Free Radic Res. 2017 Jun;51(6):604-615. doi: 10.1080/10715762.2017.1344983. Epub 2017 Jul 13.

Abstract

Aim: To investigate peripheral blood monocytes/macrophages (Mo/Mᴓ) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity.

Methods: One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL).

Results: Paraoxonase 2 activity in Mo/Mᴓ was significantly lower in type 2 diabetes patients (0.042 ± 0.044 vs 0.165 ± 0.133U lactonase activity/mg protein in controls, p < .0005) and decreased in the obese in all groups. It was inversely correlated to parameters of adiposity (BMI and Waist Circumference), of glucose control (blood glucose, fructosamine and HbA1c) and insulin resistance (HOMA-IR). In multivariate regression models, 15-34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S- (to 82 ± 18% of the cells incubated with serum, S+) and PON2 activity (from 0.524 ± 0.061 in S - to 0.298 ± 0.048 U/mg protein). In contrast, when LDL was added, the RB remained lower (61 ± 12% of S+, p = .03) and PON2 higher (0.580 ± 0.030 U/mg protein, p = .003).

Conclusions: The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified.

Keywords: Monocytes/macrophages; obesity; paraoxonase 2; respiratory burst; type 2 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Adipose Tissue / enzymology
  • Adipose Tissue / pathology
  • Adult
  • Alanine Transaminase / blood
  • Aryldialkylphosphatase / genetics
  • Aryldialkylphosphatase / metabolism*
  • Aspartate Aminotransferases / blood
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cholesterol, VLDL / blood
  • Cholesterol, VLDL / pharmacology*
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Obesity / enzymology*
  • Obesity / genetics
  • Obesity / pathology
  • Reactive Oxygen Species / metabolism
  • Respiratory Burst / drug effects*
  • Triglycerides / blood
  • U937 Cells
  • gamma-Glutamyltransferase / blood

Substances

  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cholesterol, VLDL
  • Glycated Hemoglobin A
  • Reactive Oxygen Species
  • Triglycerides
  • hemoglobin A1c protein, human
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Aryldialkylphosphatase
  • PON2 protein, human