|Role of sulfhydryl-dependent dimerization of soluble guanylyl cyclase in relaxation of porcine coronary artery to nitric oxide|
|Zheng, Xiaoxu1; Ying, Lei1; Liu, Juan1; Dou, Dou1,3; He, Qiong1; Leung, Susan Wai Sum2; Man, Ricky Y. K.2; Vanhoutte, Paul M.2; Gao, Yuansheng1,3|
|关键词||Soluble guanylyl cyclase cGMP-dependent protein kinase Disulfide bonds Vasodilatation Hypoxia|
|WOS标题词||Science & Technology|
|类目[WOS]||Cardiac & Cardiovascular Systems|
|研究领域[WOS]||Cardiovascular System & Cardiology|
|关键词[WOS]||DISULFIDE BOND FORMATION ; PROTEIN-KINASE-G ; SMOOTH-MUSCLE ; THIOL OXIDATION ; SUPEROXIDE-DISMUTASE ; NITRATE TOLERANCE ; REDOX REGULATION ; LIPOIC ACID ; DITHIOTHREITOL ; GLUTATHIONE|
Aims 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.
Conclusion These 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.
|项目编号||30770789 ; 30870938 ; 30900511 ; 777507M|
|资助机构||National Natural Science Foundation of China ; Hong Kong Research Grant Council (University of Hong Kong)|
|作者单位||1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China|
2.Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China
3.Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100871, Peoples R China
|Zheng, Xiaoxu,Ying, Lei,Liu, Juan,et al. Role of sulfhydryl-dependent dimerization of soluble guanylyl cyclase in relaxation of porcine coronary artery to nitric oxide[J]. CARDIOVASCULAR RESEARCH,2011,90(3):565-572.|
|APA||Zheng, Xiaoxu.,Ying, Lei.,Liu, Juan.,Dou, Dou.,He, Qiong.,...&Gao, Yuansheng.(2011).Role of sulfhydryl-dependent dimerization of soluble guanylyl cyclase in relaxation of porcine coronary artery to nitric oxide.CARDIOVASCULAR RESEARCH,90(3),565-572.|
|MLA||Zheng, Xiaoxu,et al."Role of sulfhydryl-dependent dimerization of soluble guanylyl cyclase in relaxation of porcine coronary artery to nitric oxide".CARDIOVASCULAR RESEARCH 90.3(2011):565-572.|
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