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cGMP is a second messenger that produces its effects by interacting with intracellular receptor proteins. In smooth muscle cells, one of the major receptors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of physiologically relevant proteins whose function(More)
Nitric oxide (NO) plays an important role as a cell-signalling molecule, anti-infective agent and, as most recently recognised, an antioxidant. The metabolic fate of NO gives rise to a further series of compounds, collectively known as the reactive nitrogen species (RNS), which possess their own unique characteristics. In this review we discuss this(More)
This basic science review examines the role of cGMP and cGMP-dependent protein kinase (PKG) in the regulation of vascular smooth muscle cell (VSMC) phenotype. The first such studies suggested a role for nitric oxide (NO) and atrial natriuretic peptides (ANP), and the downstream second messenger cGMP, in the inhibition of VSMC proliferation. Subsequently,(More)
Endothelium dysfunction with severe pulmonary hypertension may occur after total cardiopulmonary bypass (CPB) in infants as a result of a widespread inflammatory response. The aim of this study was to separate out the effects of lung ischemia-reperfusion from membrane oxygenator-induced activation of leukocytes on the function and viability of the pulmonary(More)
cGMP-dependent protein kinase (PKG) expression is highly variable and decreases in cultured vascular smooth muscle cells (VSMCs), exposure of cells to nitric oxide (NO), or in response to balloon catheter injury in vivo. In this study, the mechanisms of human type I PKG-alpha (PKG-Ialpha) gene expression were examined. Three structurally unrelated NO donors(More)
Cyclic GMP-dependent protein kinase I plays a pivotal role in regulating smooth muscle cell relaxation, growth, and differentiation. Expression of the enzyme varies greatly in smooth muscle and in other tissues and cell types, yet little is known regarding the mechanisms regulating cGMP-dependent protein kinase gene expression. The present work was(More)
NO and cGMP have antigrowth and anti-inflammatory effects on the vessel wall in response to injury. It is well established that after vascular injury proinflammatory cytokines are involved in vascular wall remodeling. The purpose of this study was to ascertain the signaling mechanisms involved in cGMP-dependent protein kinase (PKG) suppression by(More)
BACKGROUND Non-heartbeating-donor (NHBD) lung transplantation could help reduce the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung transplantation. METHODS The effect(More)
The ability of the endothelium to produce nitric oxide, which induces generation of cyclic guanosine monophosphate (cGMP) that activates cGMP-dependent protein kinase (PKG-I), in vascular smooth muscle cells (VSMCs), is essential for the maintenance of vascular homeostasis. Yet, disturbance of this nitric oxide/cGMP/PKG-I pathway has been shown to play an(More)
The transcriptional activator β-catenin is a key mediator of the canonical Wnt signaling pathway. β-catenin itself does not bind DNA but functions via interaction with T-cell factor (TCF)/lymphoid-enhancing factor (LEF) transcription factors. Thus, in the case of active Wnt signaling, β-catenin, in cooperation with TCF/LEF proteins family, activates the(More)