Premium
Roles for Cytosolic NADPH Redox in Regulating Pulmonary Artery Relaxation by Thiol Oxidation‐Elicited Subunit Dimerization of Protein Kinase G 1α
Author(s) -
Neo Boon Hwa,
Kandhi Sharath,
Wolin Michael S.
Publication year - 2012
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.26.1_supplement.873.16
Subject(s) - thioredoxin , cytosol , redox , thioredoxin reductase , phosphorylation , protein kinase a , kinase , biochemistry , biophysics , biology , chemistry , oxidative stress , enzyme , organic chemistry
The activity of glucose‐6‐phosphate dehydrogenase (G6PD) appears to control a vascular smooth muscle relaxation regulated via cytosolic NADPH oxidation. Since our studies suggest thiol oxidation‐elicited dimerization of protein kinase G 1α (PKG1α) contributes to the relaxation of endothelium‐removed bovine pulmonary arteries (BPA) to H 2 O 2 and responses to hypoxia, we investigated if cytosolic NADPH oxidation promoted relaxation by PKG1α dimerization. Depletion of PKG1α by siRNA inhibited relaxation of BPA to 6‐aminonicotinamide (6‐AN), and attenuated the increase in vasodilator‐stimulated phosphoprotein (VASP) phosphorylation. Relaxation to 6‐AN was not altered by depletion of soluble guanylate cyclase. Depletion of G6PD in BPA with siRNA increased PKG1α dimerization and VASP phosphorylation, and inhibited force generation under hypoxia. Depletion of thioredoxin‐1 and thioredoxin reductase‐1 with siRNA elicited responses similar to G6PD depletion. Thus, cytosolic NADPH redox appears to control relaxation of BPA by PKG1α dimerization through its influence on thioredoxin‐1 redox, and these processes may contribute to vascular responses to hypoxia that are associated with changes in NADPH redox. Supported by NIH grants HL031069, HL043023 and HL066331