Monocyte NADPH oxidase subunit p22(phox) and inducible hemeoxygenase-1 gene expressions are increased in type II diabetic patients: relationship with oxidative stress.
Oxidative stress is associated with diabetes mellitus: a role of vascular NADPH oxidase as a source of superoxide has been demonstrated. We determined whether in type 2 diabetes mononuclear cells, NADPH oxidase and the inducible hemeoxygenase (HO-1) gene expressions are activated. In monocytes from 25 outpatients with type 2 diabetes, p22(phox) gene expression was higher (0.71 +/- 0.09 p22(phox)/beta-actin gene expression ratio) than that observed in 19 controls (0.56 +/- 0.09, P < 0.001). Similarly, HO-1 gene expression was significantly higher in diabetic patients (0.77 +/- 0.12 HO-1/beta-actin gene expression ratio) than in controls (0.41 +/- 0.14, P < 0.001). The p22(phox) and HO-1 gene expressions were also determined during (plasma glucose 363 +/- 40 mg/dl) and after (125 +/- 11 mg/dl) metabolic decompensation in 10 type 2 diabetic patients. The correction of the metabolic milieu was associated with a 19% +/- 3% (P < 0.01) and 30% +/- 3% (P < 0.01) decrease in the p22(phox) and HO-1 gene expressions, respectively. In a multivariate analysis, age was independently associated to p22(phox) gene expression in circulating monocytes in type 2 diabetics [13% (adjusted R(2)), P < 0.05]. Decompensated type 2 diabetes is associated with increased p22(phox) and HO-1 gene expressions in circulating monocytes; the metabolic normalization reduces but does not normalize this activation. These findings suggest that these cells, which play a crucial role in the earliest events of atherosclerotic lesion, are subjected to an increased oxidative stress.
Avogaro
Angelo
A
Department of Clinical and Experimental Medicine, University of Padova, School of Medicine, Italy. angelo.avogaro@unipd.it
Pagnin
Elisa
E
Calò
Lorenzo
L
D000199:Actins / Q000235:genetics; D000368:Aged; D000375:Aging; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D004789:Enzyme Activation; D015870:Gene Expression; D006442:Glycated Hemoglobin / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology*; D009252:NADPH Dehydrogenase / Q000235:genetics*; D019255:NADPH Oxidases; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000235:genetics*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009252:NADPH Dehydrogenase; D019255:NADPH Oxidases; D010750:Phosphoproteins; C496541:HMOX1 protein, human; C086986:CYBA protein, human