IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
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
刊名CARDIOVASCULAR RESEARCH
2011-06-01
DOI10.1093/cvr/cvr016
90期:3页:565-572
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
资助者National Natural Science Foundation of China ; Hong Kong Research Grant Council (University of Hong Kong) ; National Natural Science Foundation of China ; Hong Kong Research Grant Council (University of Hong Kong)
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
英文摘要

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.

语种英语
所属项目编号30770789 ; 30870938 ; 30900511 ; 777507M
资助者National Natural Science Foundation of China ; Hong Kong Research Grant Council (University of Hong Kong) ; National Natural Science Foundation of China ; Hong Kong Research Grant Council (University of Hong Kong)
WOS记录号WOS:000290820200023
Citation statistics
Cited Times:15[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63975
Collection北京大学基础医学院_心血管所
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
Recommended Citation
GB/T 7714
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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