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Potential Role of a Thiol Oxidation‐Elicited Subunit Dimerization Activation of Protein Kinase G in the Relaxation of Pulmonary Arteries to Hydrogen Peroxide
Author(s) -
Neo Boon Hwa,
Kandhi Sharath,
Wolin Michael
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.1002.6
Subject(s) - dithiothreitol , chemistry , hydrogen peroxide , phosphoprotein , phosphorylation , cgmp dependent protein kinase , protein kinase a , thiol , protein subunit , vasodilation , kinase , serine , biophysics , biochemistry , endocrinology , enzyme , biology , mitogen activated protein kinase kinase , gene
We have previously provided evidence that hydrogen peroxide (H 2 O 2 ) stimulates soluble guanylate cyclase under conditions where it relaxes isolated endothelium‐removed bovine pulmonary arteries (BPA). Since it was recently reported that H 2 O 2 induces coronary vasorelaxation associated with a NO/cGMP‐independent thiol oxidation/subunit dimerization activation of protein kinase G, we investigated if this mechanism participates in the relaxation of BPA to H 2 O 2 . BPA precontracted with serotonin (incubated under hypoxia to lower endogenous H 2 O 2 ) were exposed to increasing concentrations of H 2 O 2 . It was observed that 0.1‐1 mM H 2 O 2 caused increased PKG dimerization and relaxation. These responses were associated with increased phosphorylation of vasodilator‐stimulated phosphoprotein (VASP) at the serine‐239 site known to be mediated by PKG. Treatment of BPA with 1 mM dithiothreitol attenuated PKG dimerization, VASP phosphorylation and relaxation to H 2 O 2 . Thus, a thiol oxidation‐elicited dimerization activation of PKG appears to be a contributing factor to the relaxation of BPA to H 2 O 2 . Supported by NIH grants HL31069, HL43023 and HL66331