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Potential Role of NADPH Redox in Regulating Thiol Oxidation‐Elicited Subunit Dimerization Activation of Protein Kinase G in the Relaxation of Bovine Pulmonary Arteries to Pentose Phosphate Pathway Inhibitors
Author(s) -
Neo Boon Hwa,
Wolin Michael
Publication year - 2010
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.24.1_supplement.795.5
Subject(s) - pentose phosphate pathway , cgmp dependent protein kinase , chemistry , protein kinase a , phosphorylation , protein subunit , protein kinase c , biochemistry , intracellular , enzyme , mitogen activated protein kinase kinase , glycolysis , gene
We have previously provided evidence that inhibition of glucose‐6‐phosphate dehydrogenase (G6PD) in the pentose phosphate pathway promotes oxidation of NADPH, and elicits vascular relaxation through coordinating multiple processes that lower intracellular calcium. Since it was reported that H 2 O 2 induces coronary relaxation associated with a NO/cGMP‐independent thiol oxidation/subunit dimerization activation of protein kinase G (PKG), we investigated if inhibition of G6PD activates PKG through disulfide‐mediated subunit dimerization under conditions where relaxation of isolated endothelium‐removed bovine pulmonary arteries (BPA) is observed. BPA precontracted with 20mM KCl under hypoxic conditions were exposed to either 1mM 6‐aminonicotinamide (6‐AN) or 0.5mM epiandrosterone (Epi) to inhibit G6PD. It was observed that both 6‐AN and Epi increased PKG dimerization under conditions where relaxation was observed. These responses were associated with increased phosphorylation of vasodilator‐stimulated phosphoprotein (VASP) at the serine‐239 site known to be mediated by PKG. Thus, inhibition of G6PD promotes thiol oxidation‐elicited dimerization activation of PKG, suggesting that PKG activation is likely to be a participant in mechanisms through which cytosolic NADPH oxidation promotes vascular relaxation. Supported by NIH grants HL31069, HL43023 and HL66331