Background A direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiopulmonary disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: they sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC in...

Raddeanin A (RA) is an extractive from Anemone raddeana Regel, a traditional Chinese medicine. The aim of this study is to assess the efficacy of RA against human gastric cancer (GC) cells (SGC-7901) and explore its mechanism. MTT assay showed that RA inhibition of proliferation of SGC-7901 cells increased in a dose-dependent manner. Flow cytometry analysis and Hoechst 33258 staining showed tha...

To achieve this goal, I developed a heterologous expression system of full-length bovine sGC (Fl-sGC). Early attempts to produce recombinant bovine sGC in E. coli resulted in misfolded protein accumulation. Indeed, producing soluble protein in Escherichia coli is still a major difficulty in the sGC field. By using fusion technology, I successfully overexpressed both α and β subunits in a solubl...

Methods The FRET donor, CFP, and FRET acceptor, YFP, were fused to aminoand carboxy-terminal ends of sGC subunits. After generation of recombinant baculovirus strains fluorescent tagged sGC subunits were co-expressed in Sf9cells. Fluorescent variants of sGC were analyzed in vitro in cytosolic fractions by sensitized emission FRET. In addition, fluorescent tagged sGC subunits were analyzed in vi...

the entanglement between a ?-type three-level atom and its spontaneous emission fields is investigated. the effect of spontaneously generated coherence (sgc) on entanglement between the atom and its spontaneous emission fields is then discussed. we find that in the presence of sgc the entanglement between the atom and its spontaneous emission fields is completely phase dependent, while in absen...

Nitric oxide (NO) affects many physiological systems by activating cGMP signaling cascades through soluble guanylate cyclase (sGC). In the accepted model, NO binds to the sGC heme, activating the enzyme. Here, we report that in the presence of physiological concentrations of ATP and GTP, NO dissociation from the sGC heme is approximately 160 times slower than the rate of enzyme deactivation in ...

Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme implicated in the control of smooth muscle tone that also regulates platelet aggregation. Moreover, sGC activation has been shown to reduce leukocyte adherence to the endothelium. Herein, we investigated the expression of sGC in a murine model of LPS-induced lung injury and evaluated the effects of sGC inhibition in the context of acute...

The molecular mechanism of desensitization of soluble guanylyl cyclase (sGC), the NO receptor, has long remained unresolved. Posttranslational modification and redox state have been postulated to affect sGC sensitivity to NO but evidence has been lacking. We now show that sGC can be S-nitrosylated in primary aortic smooth muscle cells by S-nitrosocysteine (CSNO), an S-nitrosylating agent, in hu...

Soluble guanylate cyclase (sGC), a key enzyme of the nitric oxide (NO) signaling pathway, is attracting rapidly growing interest as a therapeutic target in cardiopulmonary disease, with several sGC agonists currently in clinical development. On binding of NO to a prosthetic heme group on sGC, the enzyme catalyzes synthesis of the second messenger cGMP, which produces vasorelaxation and inhibits...