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Expression of functionally phagocyte‐type NAD(P)H oxidase in pericytes: effect of angiotensin II and high glucose
Author(s) -
Manea Adrian,
Raicu Monica,
Simionescu Maya
Publication year - 2005
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1042/bc20040107
Subject(s) - nadph oxidase , nad+ kinase , nad(p)h oxidase , angiotensin ii , biology , superoxide , oxidase test , reactive oxygen species , phagocyte , endocrinology , oxidative stress , medicine , p22phox , biochemistry , microbiology and biotechnology , enzyme , receptor , phagocytosis
Background information . A growing body of evidence demonstrates the involvement of the oxidative stress in the development of vascular complications associated with diabetes, such as hypertension, retinopathy, nephropathy, neuropathy and atherosclerosis. However, the molecular mechanisms accountable for the increased production of reactive oxygen species (ROS) remain uncertain. Among others, the NAD(P)H oxidase is one of the most important sources of superoxide anion (O 2 − ) that induce dysfunction of vascular cells. Pericytes (PCs) have an essential role in the capillary dysfunction in retinopathy and other vascular complications in diabetes. We questioned whether PCs express a functional phagocyte‐type NAD(P)H oxidase, and examined the role of angiotensin II and high glucose on the activity of the oxidase complex and expression of the essential subunit p22 phox . Results . The mRNA expression of p22 phox , p47 phox , p67 phox and NOX 1 subunits, and the lack of gp91 phox component, were detected in PCs by reverse transcriptase PCR. Western‐blotting analysis demonstrated the protein expression of p22 phox , p47 phox and p67 phox subunits. As compared with the normal condition, stimulation of PCs with angiotensin II or high glucose induced: (i) an increase in ROS production and NAD(P)H oxidase activity, and (ii) an up‐regulation of p22 phox mRNA and protein expression. Conclusions . Taken together, the present study provides the first evidence that PCs express a functional phagocyte‐type NAD(P)H oxidase, which is up‐regulated by both angiotensin II and high glucose. Given the importance of ROS in vascular physiology and pathology, the NAD(P)H oxidase complex could be an important therapeutic target in the treatment of microvascular disorders.