title: H2O2 regulation of vascular function through sGC mRNA stabilization by HuR.
abstract: OBJECTIVE
  Hydrogen peroxide (H(2)O(2)) is an important mediator in the vasculature, but its role in the regulation of soluble guanylate cyclase (sGC) activity and expression is not completely understood. The aim of this study was to test the effect of H(2)O(2) on sGC expression and function and to explore the molecular mechanism involved.
  
  
  RESULTS
  H(2)O(2) increased sGCβ1 protein steady-state levels in rat aorta and aortic smooth muscle cells (RASMCs) in a time- and dose-dependent manner, and this effect was blocked by catalase. sGCα2 expression increased along with β1 subunit, whereas α1 subunit remained unchanged. Vascular relaxation to an NO donor (sodium nitroprusside) was enhanced by H(2)O(2), and it was prevented by ODQ (sGC inhibitor). cGMP production in both freshly isolated vessels and RASMCs exposed to H(2)O(2) was greatly increased after sodium nitroprusside treatment. The H(2)O(2)-dependent sGCβ1 upregulation was attributable to sGCβ1 mRNA stabilization, conditioned by the translocation of the mRNA-binding protein HuR from the nucleus to the cytosol, and the increased mRNA binding of HuR to the sGCβ1 3' untranslated region. HuR silencing reversed the effects of H(2)O(2) on sGCβ1 levels and cGMP synthesis.
  
  
  CONCLUSIONS
  Our results identify H(2)O(2) as an endogenous mediator contributing to the regulation of vascular tone and point to a key role of HuR in sGCβ1 mRNA stabilization.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Abel
authors.initials: A
authors.lastname: Martín-Garrido
authors.forename: Marta
authors.initials: M
authors.lastname: González-Ramos
authors.forename: Mercedes
authors.initials: M
authors.lastname: Griera
authors.forename: Brenda
authors.initials: B
authors.lastname: Guijarro
authors.forename: Jorge
authors.initials: J
authors.lastname: Cannata-Andia
authors.forename: Diego
authors.initials: D
authors.lastname: Rodriguez-Puyol
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Puyol
authors.forename: Marta
authors.initials: M
authors.lastname: Saura
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D001665:Binding Sites; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D021381:Protein Transport; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013997:Time Factors; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; D006861:Hydrogen Peroxide; D002374:Catalase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP