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

• Published in: Free radical research Vol. 51; no. 6; pp. 604 - 615
• Main Authors: Lixandru, D., Alexandru, P., Mihai, A., Roşca, A., Ionescu-Tîrgovişte, C., Braşoveanu, L.I., Manuel-y-Keenoy, B.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.06.2017
• Subjects: 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; gamma-Glutamyltransferase - blood; Glycated Hemoglobin A - metabolism; Humans; Insulin Resistance; Male; Middle Aged; Monocytes/macrophages; obesity; Obesity - enzymology; Obesity - genetics; Obesity - pathology; paraoxonase 2; Reactive Oxygen Species - metabolism; respiratory burst; Respiratory Burst - drug effects; Triglycerides - blood; type 2 diabetes; U937 Cells; paraoxonase 2; Monocytes/macrophages; type 2 diabetes; obesity; respiratory burst
• ISSN: 1071-5762; 1029-2470; 1029-2470
• DOI: 10.1080/10715762.2017.1344983

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 HbA 1c ) 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.