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Decreased Protein Kinase G Activation by Disulfide‐Mediated Subunit Dimerization is Observed when Hypoxia Promotes Contraction of Bovine Pulmonary Arteries
Author(s) -
Neo Boon Hwa,
Kandhi Sharath,
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.795.4
Subject(s) - chemistry , dithiothreitol , hypoxia (environmental) , contraction (grammar) , protein kinase a , cgmp dependent protein kinase , medicine , phosphorylation , endocrinology , rho associated protein kinase , vasodilation , biophysics , biochemistry , oxygen , biology , enzyme , mitogen activated protein kinase kinase , organic chemistry
Our laboratory had 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), and that hypoxia promotes BPA contraction through suppressing relaxation by endogenous H 2 O 2 . 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 this mechanism participates in the contraction of BPA to hypoxia. BPA precontracted with 20 mM KCl showed decreased PKG dimerization in arteries exposed to hypoxia (PO 2 ~10 torr) versus BPA contracted under aerobic conditions (21% O 2 ). Hypoxia also promoted decreased phosphorylation of vasodilator‐stimulated phosphoprotein (VASP) at the serine‐239 site known to be mediated by PKG. Treatment of BPA with 1 mM dithiothreitol increased potassium contraction and abolished contraction to hypoxia, under conditions where it prevented PKG dimerization. Interestingly, serotonin was observed to increase PKG dimerization under hypoxic conditions in a manner which may be related to its oxidase activation‐associated promotion of pulmonary artery smooth muscle remodeling. Thus, attenuation of PKG activation by disulfide‐mediated dimerization appears to be a contributing factor to the contraction of BPA by hypoxia.