Roles for cytosolic NADPH redox in regulating pulmonary artery relaxation by thiol oxidation-elicited subunit dimerization of Protein Kinase G 1α

Roles for cytosolic NADPH redox in regulating pulmonary artery relaxation by thiol oxidation-elicited subunit dimerization of Protein Kinase G 1α
Am J Physiol Heart Circ Physiol. 2013 May 24;
Authors: Neo BH, Patel D, Kandhi S, Wolin MS
Abstract
The activity of glucose-6-phosphate dehydrogenase (G6PD) appears to control a vascular smooth muscle relaxing mechanism regulated through cytosolic NADPH oxidation. Since our recent studies suggest thiol oxidation-elicited dimerization of the 1α form of protein kinase G (PKG1α) contributes to the relaxation of isolated endothelium-removed bovine pulmonary arteries (BPA) to peroxide and responses to hypoxia, we investigated if cytosolic NADPH oxidation promoted relaxation by PKG1α dimerization. Relaxation of BPA to G6PD inhibitors, 6-aminonicotinamide (6-AN) and epiandrosterone (studied under hypoxia to minimize basal levels of NADPH oxidation and PKG1α dimerization) was associated with increased PKG1α dimerization and PKG-mediated vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Depletion of PKG1α by siRNA inhibited relaxation of BPA to 6-AN, and attenuated the increase in VASP phosphorylation. Relaxation to 6-AN did not appear to be altered by depletion of sGC. Depletion of G6PD, thioredoxin-1 (Trx) and Trx reductase-1 (TrxR-1) in BPA with siRNA increased PKG1α dimerization and VASP phosphorylation, and inhibited force generation under aerobic and hypoxic conditions. Depletion of ...

Source: American Journal of Physiology. Heart and Circulatory Physiology - May 24, 2013 Category: Physiology Authors: Neo BH, Patel D, Kandhi S, Wolin MS Tags: Am J Physiol Heart Circ Physiol Source Type: research