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Article: Role of sulfhydryl-dependent dimerization of soluble guanylyl cyclase in relaxation of porcine coronary artery to nitric oxide

TitleRole of sulfhydryl-dependent dimerization of soluble guanylyl cyclase in relaxation of porcine coronary artery to nitric oxide
Authors
KeywordscGMP-dependent protein kinase
Disulfide bonds
Hypoxia
Soluble guanylyl cyclase
Vasodilatation
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.org
Citation
Cardiovascular Research, 2011, v. 90 n. 3, p. 565-572 How to Cite?
AbstractAims Soluble guanylyl cyclase (sGC) is a heterodimer. The dimerization of the enzyme is obligatory for its function in mediating actions caused by agents that elevate cyclic guanosine monophosphate (cGMP). The present study aimed to determine whether sGC dimerization is modulated by thiol-reducing agents and whether its dimerization influences relaxations in response to nitric oxide (NO). Methods and results The dimers and monomers of sGC and cGMP-dependent protein kinase (PKG) were analysed by western blotting. The intracellular cGMP content was measured by enzyme-linked immunosorbent assay. Changes in isometric tension were determined in organ chambers. In isolated porcine coronary arteries, the protein levels of sGC dimer were decreased by the thiol reductants dithiothreitol, l-cysteine, reduced l-glutathione and tris(2-carboxyethyl) phosphine. The effect was associated with reduced cGMP elevation and attenuated relaxations in response to nitric oxide donors. The dimerization of sGC and activation of the enzyme were also decreased by dihydrolipoic acid, an endogenous thiol antioxidant. Dithiothreitol at concentrations markedly affecting the dimerization of sGC had no significant effect on the dimerization of PKG or relaxation in response to 8-Br-cGMP. Relaxation of the coronary artery in response to a NO donor was potentiated by hypoxia when sGC was partly inhibited, coincident with an increase in sGC dimer and enhanced cGMP production. These effects were prevented by dithiothreitol and tris(2-carboxyethyl) phosphine. ConclusionThese results demonstrate that the dimerization of sGC is exquisitely sensitive to thiol reductants compared with that of PKG, which may provide a novel mechanism for thiol-dependent modulation of NO-mediated vasodilatation in conditions such as hypoxia. © The Author 2011.
Persistent Identifierhttp://hdl.handle.net/10722/135351
ISSN
2015 Impact Factor: 5.465
2015 SCImago Journal Rankings: 2.897
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30770789
30870938
30900511
Hong Kong Research Grant Council (University of Hong Kong)777507M
Funding Information:

This work was supported in part by the National Natural Science Foundation of China grant no. 30770789, 30870938, and 30900511 and the Hong Kong Research Grant Council (University of Hong Kong-777507M).

References

 

DC FieldValueLanguage
dc.contributor.authorZheng, Xen_HK
dc.contributor.authorYing, Len_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorDou, Den_HK
dc.contributor.authorHe, Qen_HK
dc.contributor.authorLeung, SWSen_HK
dc.contributor.authorMan, RYKen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorGao, Yen_HK
dc.date.accessioned2011-07-27T01:33:58Z-
dc.date.available2011-07-27T01:33:58Z-
dc.date.issued2011en_HK
dc.identifier.citationCardiovascular Research, 2011, v. 90 n. 3, p. 565-572en_HK
dc.identifier.issn0008-6363en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135351-
dc.description.abstractAims Soluble guanylyl cyclase (sGC) is a heterodimer. The dimerization of the enzyme is obligatory for its function in mediating actions caused by agents that elevate cyclic guanosine monophosphate (cGMP). The present study aimed to determine whether sGC dimerization is modulated by thiol-reducing agents and whether its dimerization influences relaxations in response to nitric oxide (NO). Methods and results The dimers and monomers of sGC and cGMP-dependent protein kinase (PKG) were analysed by western blotting. The intracellular cGMP content was measured by enzyme-linked immunosorbent assay. Changes in isometric tension were determined in organ chambers. In isolated porcine coronary arteries, the protein levels of sGC dimer were decreased by the thiol reductants dithiothreitol, l-cysteine, reduced l-glutathione and tris(2-carboxyethyl) phosphine. The effect was associated with reduced cGMP elevation and attenuated relaxations in response to nitric oxide donors. The dimerization of sGC and activation of the enzyme were also decreased by dihydrolipoic acid, an endogenous thiol antioxidant. Dithiothreitol at concentrations markedly affecting the dimerization of sGC had no significant effect on the dimerization of PKG or relaxation in response to 8-Br-cGMP. Relaxation of the coronary artery in response to a NO donor was potentiated by hypoxia when sGC was partly inhibited, coincident with an increase in sGC dimer and enhanced cGMP production. These effects were prevented by dithiothreitol and tris(2-carboxyethyl) phosphine. ConclusionThese results demonstrate that the dimerization of sGC is exquisitely sensitive to thiol reductants compared with that of PKG, which may provide a novel mechanism for thiol-dependent modulation of NO-mediated vasodilatation in conditions such as hypoxia. © The Author 2011.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.orgen_HK
dc.relation.ispartofCardiovascular Researchen_HK
dc.subjectcGMP-dependent protein kinaseen_HK
dc.subjectDisulfide bondsen_HK
dc.subjectHypoxiaen_HK
dc.subjectSoluble guanylyl cyclaseen_HK
dc.subjectVasodilatationen_HK
dc.subject.meshCoronary Vessels - drug effects - enzymology - physiology-
dc.subject.meshCyclic GMP-Dependent Protein Kinases - chemistry - physiology-
dc.subject.meshGuanylate Cyclase - chemistry - physiology-
dc.subject.meshReceptors, Cytoplasmic and Nuclear - chemistry - physiology-
dc.subject.meshVasodilation - drug effects - physiology-
dc.titleRole of sulfhydryl-dependent dimerization of soluble guanylyl cyclase in relaxation of porcine coronary artery to nitric oxideen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, SWS: swsleung@hku.hken_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityLeung, SWS=rp00235en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/cvr/cvr016en_HK
dc.identifier.pmid21248051-
dc.identifier.scopuseid_2-s2.0-79957449176en_HK
dc.identifier.hkuros187139en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79957449176&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume90en_HK
dc.identifier.issue3en_HK
dc.identifier.spage565en_HK
dc.identifier.epage572en_HK
dc.identifier.eissn1755-3245-
dc.identifier.isiWOS:000290820200023-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridZheng, X=23013502000en_HK
dc.identifier.scopusauthoridYing, L=35783476900en_HK
dc.identifier.scopusauthoridLiu, J=53264432500en_HK
dc.identifier.scopusauthoridDou, D=23011481300en_HK
dc.identifier.scopusauthoridHe, Q=36192855300en_HK
dc.identifier.scopusauthoridLeung, SWS=24540419500en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridGao, Y=35767818500en_HK

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