title: Sulfhydryl-dependent dimerization and cGMP-mediated vasodilatation.
abstract: Sulfhydryl-dependent formation of interprotein disulfide bonds in response to physiological oxidative stimuli is emerging as an important mechanism in the regulation of various biological activities. Soluble guanylyl cyclase (sGC) and cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) are key enzymes for actions caused by cGMP-elevating agents, including nitric oxide (NO). Both sGC and PKG are dimers. The dimerization of sGC is obligatory for its activity, whereas the dimerization of PKG improving its signaling efficacy. sGC dimerization is decreased by endogenous and exogenous thiol reductants, associated with reduced cGMP elevation and attenuated vasodilatation to NO. The dimerization of PKG Iα is increased by oxidative stress, coincident with improved PKG signaling and augmented vasodilatation to NO. In coronary arteries, the dimerizations and activities of sGC and PKG are increased by hypoxia, accompanied by enhanced relaxation induced by NO. In contrast, the dimerizations and activities of these enzymes and NO-induced relaxation of pulmonary arteries are reduced by hypoxia. These opposite effects may result from divergent changes in the redox status of cytoplasmic reduced nicotinamide adenine dinucleotide phosphate between coronary and pulmonary arteries in response to hypoxia.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
authors.forename: Dou
authors.initials: D
authors.lastname: Dou
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zheng
authors.forename: Lei
authors.initials: L
authors.lastname: Ying
authors.forename: Liping
authors.initials: L
authors.lastname: Ye
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D004220:Disulfides; D013438:Sulfhydryl Compounds; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP