Premium
Inhibition of NADPH oxidase restores NO availability and migratory function in diabetic CD34 cells
Author(s) -
Jarajapu Yagna,
Verma Amrisha,
Kent David,
Li Qiuhong,
Grant Maria
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.937.2
Subject(s) - apocynin , nadph oxidase , cd34 , progenitor cell , chemistry , nox4 , endothelial progenitor cell , reactive oxygen species , microbiology and biotechnology , stem cell , biology , biochemistry
Migration of circulating endothelial progenitor cells (CD34) to sites of vascular injury is critical for the reparative function and is mediated by NO. CD34 cell migration is defective in diabetes. Production of reactive oxygen species (ROS) by NADPH oxidase (NOX) is known to decrease NO availability involving endothelial dysfunction. We hypothesized that migratory defect in diabetic CD34 cells could be corrected by the inhibition of NOX. Peripheral blood was obtained from healthy and Type 1‐diabetic individuals and CD34 cells were isolated by immunomagnetic selection. Real time PCR detected higher expression of NOX2 mRNA in diabetic CD34 cells. Diabetic CD34 cells showed increased ROS production and decreased NO release in response to SDF1 (100 nM). Apocynin (300 µM) treatment decreased ROS production and increased NO release. Similar effects were observed with pretreatment of cells with gp91ds‐tat that selectively inactivates gp91phox. Pretreatment with apocynin or gp91ds‐tat increased migration of diabetic CD34 cells in response to SDF1 and VEGF (25 ng/ml). These results suggest that pretreatment of diabetic CD34 cells with NOX inhibitors may enhance their ability of in vivo engraftment.