Soluble guanylyl cyclase (sGC) is the major physiological target of sydnonimine-based vasodilators such as molsidomine. Decomposition of sydnonimines results in the stoichiometric formation of nitric oxide (NO) and superoxide (O2-), which rapidly react to form peroxynitrite. Inasmuch as sGC is activated by NO but not by peroxynitrite, we investigated the mechanisms underlying sGC activation by ...

Background Following prolonged exposure to NO, soluble guanylyl cyclase (sGC) becomes desensitized and fails to respond to additional NO stimulation. We showed that sGC is desensitized by S-nitrosylation in vitro, in primary smooth muscle cells (SMC) and in tissues and identified two cysteines (Cys) targeted by this post-translational modification that are involved in sGC desensitization [1]. W...

BACKGROUND The effectiveness of chemotherapy for gastric cancer is largely limited by either intrinsic or acquired drug resistance. In this study, we aimed to explore the association between miR-30a dysregulation and multidrug resistance (MDR) in gastric cancer cells. MATERIAL AND METHODS We recruited 20 patients with advanced gastric cancer. Chemosensitivity was assessed after completion of th...

Ailanthone is a major quassinoid extracted from the Chinese medicinal herb Ailanthus altissima, which has been reported to exert antiproliferative effects on various cancer cells. The present study aimed to investigate the antitumor effects of ailanthone on SGC‑7901 cells, and to analyze its underlying molecular mechanisms. Following treatment with ailanthone, Cell Counting kit‑8 was used to de...

Soluble guanylyl cyclase (sGC) is the principal receptor for NO and plays a ubiquitous role in regulating cellular function. This is exemplified in the cardiovascular system where sGC governs smooth muscle tone and growth, vascular permeability, leukocyte flux, and platelet aggregation. As a consequence, aberrant NO-sGC signaling has been linked to diseases including hypertension, atheroscleros...

The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophasphate (cGMP)-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular in chronic renal failure. Thus, the pool of heme free sGC is increased under pathological conditions. sGC activators such as cinaciguat selectiv...

Soluble guanylyl cyclase (sGC) is the major cytosolic receptor for nitric oxide (NO) that converts GTP into the second messenger cGMP in a NO-dependent manner. Other factors controlling this key enzyme are intracellular proteins such as Hsp90 and PSD95, which bind to sGC and modulate its activity, stability, and localization. To date little is known about the effects of posttranslational modifi...

Nitric oxide (NO) is the principal mediator of penile erection, and PDE-5 inhibitors are the first-line agents used to treat erectile dysfunction (ED). When NO formation or bioavailability is decreased by oxidative stress and PDE-5 inhibitors are no longer effective, a new class of agents called soluble guanylate cyclase (sGC) stimulators like BAY 41-8543 will induce erection. sGC stimulators b...

Nitric oxide (NO) regulates a number of essential physiological processes by activating soluble guanylate cyclase (sGC) to produce the second messenger cGMP. The mechanism of NO sensing was previously thought to result exclusively from NO binding to the sGC heme; however, recent studies indicate that heme-bound NO only partially activates sGC and additional NO is involved in the mechanism of ma...

OBJECTIVE The subgenual cingulate (SGC) cortex has been implicated in the pathophysiology of mood disorders. We sought to study morphometric characteristics of the SGC in pediatric subjects with familial bipolar disorder (BD) compared with healthy controls. METHOD Twenty children and adolescents with BD (mean age = 14.6 years, 4 females) and 20 healthy age-, gender-, and intelligence quotient...