Glucose‐6‐phosphate dehydrogenase deficiency promotes endothelial oxidant stress and decreases endothelial nitric oxide bioavailability

SPECIFIC AIMSThe vascular endothelium responds to local oxidant stress by increasing the activity of antioxidant enzymes such as glucose-6-phosphate dehydrogenase (G6PD), the first enzyme in the pentose phosphate pathway and the principal source of cellular NADPH. NADPH is used as an intracellular reducing equivalent to protect against oxidative injury in addition to a cofactor for nitric oxide synthase (NOS) activity. In this study, we examined the role of deficient G6PD activity on cellular oxidant stress and NOS activity in aortic endothelial cells.PRINCIPAL FINDINGS1. Inhibition of G6PD activity promotes endothelial cell oxidant stressBovine aortic endothelial cells (BAEC) were treated with dehydroepiandrosterone (DHEA) (100 μM), a noncompetitive inhibitor of G6PD. Treatment with DHEA for 24 h significantly decreased G6PD activity (116.6±6.0 vs. 30.1±6.0 units/6 min/mg protein, n=6, P<0.0001), resulting in diminished NADPH stores (0.4±0.03 vs. 0.3±0.003 nmol/mg protein, n=3, P<0.03). Basal levels of r...